December 3, 2004
The Stephen Decatur House
1610 H Street, NW
Washington, DC 20006
COUNCIL MEMBERS PRESENT
Leon R. Kass, M.D., Ph.D., Chairman
American Enterprise Institute
Daniel W. Foster, M.D.
University of Texas, Southwestern Medical School
Michael S. Gazzaniga, Ph.D.
P. George, D.Phil., J.D.
Ann Glendon, J.D., L.LM.
William B. Hurlbut, M.D.
Peter A. Lawler, Ph.D.
Johns Hopkins University School of Medicine
Gilbert C. Meilaender,
Diana J. Schaub, Ph.D.
Q. Wilson, Ph.D.
University of California, Los Angeles
SESSION 5: BIOTECHNOLOGY AND PUBLIC
POLICY: THE NEW CANADIAN SYSTEM
CHAIRMAN KASS: Good morning. I think we should probably
start. I think there are a couple of our members who've indicated
that they will be coming late, but I don't think we should delay
any further. This morning we continue our attention to the subject
of the regulation of new biotechnologies. And as everybody here,
I think, knows, the Canadian Parliament last spring enacted major
legislation creating a new broad and comprehensive system of regulation
of assisted reproductive technologies. The legislation is the culmination
of a very long and careful process that was begun by the work of
Royal Commission, the chairman of which, Patricia Baird, addressed
this Council, I want to say more than two years ago.
But between activity of the Commission and the enactment of the
law, it was not an easy or simple task and we are very fortunate
to have with us some people who are heavily involved in that legislative
activity. Three gentlemen at the table, Ian Shugart, who is the
Assistant Deputy Minister of Health Canada, Health Canada being
the equivalent of our Department of Health and Human Services.
He is joined by Michael Vandergrift, who is the Director of Health
Science Policy Division and Glen Rivard, who is the general counsel
of Health Canada. Welcome to all three of you.
We had the privilege at the office, the staff and I, of hearing
a presentation by these three men about two months ago, describing
not just the content of the law but in the discussion exploring
how it was possible for them to bring this about and while Canada
and the United States, though friends, are not identical twins in
political matters, we thought that it would be extremely useful
for this body, as we continue our thoughts on regulation, to learn
about what the Canadians have done and how they did it and so thank
you very much for returning, for offering us your thoughts and we
look forward to the presentation.
MR. SHUGART: Thank you very much, Dr. Kass and it is very
much a pleasure for us to be here and to have sat in the public rows
yesterday and enjoyed and benefited enormously from the discussion of
the range of issues that you have on your agenda at this meeting. We
do appreciate the honor of being invited to present to the council and
we hope it will be useful for you and we know that it will be useful
for us as you share your views and your reactions with us. Canada/US
relations have been very much at the top of our minds over the last
week as the President visited Ottawa and Halifax and both the Prime
Minister and the President reiterated the desire of both countries to
work closely together on a range of issues and it may be that in our
own small way on this topic, we can contribute to the relationship
between Canada and the United States.
In this presentation, we intend to provide some context for the experience
that we've had in Canada, give an overview of the content of
the legislation and then provide some thoughts really drawn from
the experience that we have been through and indeed are continuing
to go through. In the presentation, I think it will be useful to
touch on some of the issues that were discussed yesterday afternoon
in the presentation by Professor Fukuyama. We'll touch, for
example, on the key role of legislators in this process. That was,
I think, an important issue that you touched on and with reference
to Dr. McHugh's comments, the Canadian Parliament didn't
set out to put up its dukes, but we certainly did deal with the
issues of research in the context of an emphasis on addressing the
health and safety implications of this particular area of biotechnology
The Chairman has referred to the history of this experience in
Canada. It has been a complex one and a long one. One might say
that it had a greater than 10-year gestation. The Canadian policy
environment had been driven by the Royal Commission on Reproductive
Technologies that was established in the late 1980s. It's interesting
to note that the Commission came about as a result of pressure from
the public to address new developments in the area of assisted human
reproduction and these technologies, particularly from women's
groups, bioethicists and geneticists, and also faith-based groups
and some others.
Since the report of the Royal Commission was tabled, Canada has
had a voluntary moratorium on a variety of practices: Regulations
governing the safety of sperm donation and their storage and three
different legislative processes. The first legislative attempt
focused only on prohibitions. It was fairly roundly criticized
on the grounds that it did not provide a regulatory framework to
deal with some of the issues that were relevant.
The second attempt was a draft bill for pre-study by a
parliamentary committee and then finally the last initiative saw
legislation passed by our Parliament in April — excuse me, March of
this year, almost two years after its first introduction. I personally
on this file have worked with three different ministers of health and
with the fourth now working on the process of the developing the
regulations to implement that act.
In the end, a key factor in achieving passage of this legislation
was the fact that it had been over 10 years since the Royal Commission
first dealt with it. For some this has been perhaps a symptom of
a broader issue in which the challenge of keeping public policy
responsive and keeping pace with developments in science and technology
is, I think, a profound challenge for our societies.
Very quickly, let me describe to you the environment for
assisted human reproduction in Canada. As a general rule of thumb, you
can take the population of Canada and other factors and multiply by 10
in the United States context. Not everything follows that rule but
it's a general idea of the size of the country. We estimate that
one in eight Canadian couples turns to AHR techniques to deal with the
problem of infertility. In 2001, over 1200 children were born in
Canada using these procedures. Most of the services are provided in
physician's offices, private clinics, which are corporately
constituted as independent commercial entities.
Approximately 25 of these centers mostly in the largest urban centers,
Vancouver, Toronto and Montreal and about 104 facilities, are involved
in either sperm distribution, importation or processing. We also
need to set as part of the context, that Canada, like the United
States, is a federation and the constitutional division of powers
is an important feature of how we have addressed the bill and also
the Charter of Rights and Freedoms which was put into our constitution
in the early 1980s is an important dimension of addressing the issue
The major aspects of the bill that we're going to refer to
and in a moment, I'll invite my colleague Glen Rivard, to give
you a brief synopsis of the different components of the bill. The
Canadian legislation contains, as we heard yesterday afternoon from
Professor Fukuyama, a Declaration of Principles, a set of prohibitions,
a number of controlled activities, and the rules by which those
controlled activities can occur, a section dealing with the reporting
of information related to health, rules for the licensing, inspection
and enforcement of the provisions of the bill, and then finally,
the establishment of the Assisted Human Reproduction Agency of Canada.
It's important to know that the legislation is
established under the criminal law head of power in our Constitution.
This gives us the ability to regulate health and safety, our Food and
Drugs Act, for example, which roughly corresponds to the legislation
governing your own Food and Drug Administration. It takes place under
the criminal law head of power. And one of the purposes of the
criminal law is to, in the rather old language, prevent a public evil
and under that category, some of the ethical dimensions of these
technologies are addressed.
Glen, I'll invite you take us briefly through the scope
of the Act and the subsequent pages.
MR. RIVARD: Thank you, Ian. The diagram in front of you
is an attempt to pictorially summarize what is and what is not covered
by the legislation and of course, the first major distinction is
to realize that the legislation focuses on assisted human reproduction
only and, in particular, this encompasses then the collection and
treatment of the gametes that would be used for these processes,
the processes surrounding artificial fertilization and then if you
will, the uses or the outcomes of that process, the uses of the
resultant embryo. The primary purpose for this, of course, under
the legislation, would be creation of embryos for reproductive purposes
and the legislation governs the treatment of that embryo and the
process of its transfer into the woman.
And it is at that point that the legislation ceases to
apply. At that point, the woman is pregnant as in any other fashion
and the legislation really has nothing more to say about the pregnancy,
the embryo within the woman, birth, anything of that sort. It's —
the legislation is concerned with and only with assisted human
There are other outcomes pertaining to, or possible outcomes with
respect to, the resultant embryo. The embryos can — artificial
embryos or embryos can only be created artificially only for the
purpose of reproduction, but given the state of the technology,
if you will, there are embryos that are surplus to that process
and the legislation does envisage as well, the ability to donate
them to third parties for reproductive purposes, research on the
very limited circumstances or the possibility of disposal of the
embryos as well.
The only notable exceptions to this framework are the provisions
that deal with surrogacy, particularly the commercial aspect of
surrogacy. And the legislation basically allows for surrogacy but
prohibits payment for surrogacy with an exception relating to expenditures.
But other than that, all the activities fall within that framework.
I'm going to focus on really four aspects of the bill, the first
being the Declaration of Principles. This serves, I suppose, many
purposes, but at least in terms of the legal use of the provision,
it really in Canadian law has two effects. The first is where there
is ambiguity in the application of the Act, a particular situation,
the courts can refer to the Declaration of Principles to provide
some guidance and secondly, the Act specifically provides that the
Agency must operate in accordance with the principles. So that
in the process of granting licenses, for example, to undertake in
vitro fertilization procedures or any other regulated procedure,
it must pay attention and apply the principles.
The — the principles are not organized in — there's
no priority to the principles with one exception and, therefore,
the process of applying them will be a matter of considering the
ones that are relevant to the particular decision and balancing
of these factors. The one exception is the first principle where
the language explicitly gives priority to the health and well-being
of children who would be created as a result of these procedures.
The other principles of importance include the benefit —
reference to the benefits of the technology and the need to protect
health, safety, dignity and rights. As well, there's a reference
to the protection of the health and well-being of women, importance
given to free and informed consent as a fundamental principle for these
activities, reference to non-discrimination, a reference to the
concerns relating to commercialization of donations, for example, and a
principle pertaining to the need to protect the integrity of the human
As Ian mentioned, the legislation is based on the criminal law power,
which under the Canadian Constitution is an exclusive federal jurisdiction
and therefore, makes it relatively easy for us to pass legislation
that's applicable across the country. The criminal law power
has a rather wider interpretation — wide interpretation in
Canada. It includes the ability, of course, to legislate with respect
to matters of public morality, which is what most people think of
when they think of criminal law, but it has also been interpreted
by the courts to include legislation with the purpose of protecting
health and safety of Canadians and it's under that heading,
for example, that we regulate food and drugs under our Food and
This is very similar in approach. The legislation can be
conceived of achieving two objectives. The first is the — the first
objective is really that covered by the prohibitions in which we set
out limitations on activities, limitations that are primarily driven by
ethical concerns and the second pertains to provisions that are
intended to protect the health and safety of those participating in
activities that are deemed to be basically ethical and those are the
controlled activities and we'll come to that very shortly. But
just to quickly run through the prohibitions, you can see that — I
won't go into great detail on all of them, but clearly human
cloning is prohibited. All forms of human cloning and for any purpose
is prohibited under this legislation, as is germ-line genetic
alteration. Sex selection for non-medical purposes is prohibited.
There has been some, I know, concern around this Commission about
phenomenon such as the parentless child. There is a prohibition
against creating an embryo from a cell of another embryo or fetus.
The — an artificially created embryo must be implanted within
a woman within 14 days to — we were quite concerned about
the notion of embryos developing sort of to who-knows what end point
outside the body of a woman. The 14 days is 14 developmental days.
So if the embryo is frozen as is typically the case in the in vitro
fertilization process, the clock stops ticking on that particular
provision. There are also, again, provisions dealing with prohibiting
chimeras and hybrids for most purposes, for reproductive purposes.
And again, I've mentioned in the past, commercialization of
the reproductive capacities of individuals, this — there's
no prohibition against commercialization of the industry and this
is a common misunderstanding. It is a private sector industry as
it were, and that's not affected by this except that there are
provisions that address the reproductive capacities of individuals
who deal with — who basically make it illegal to pay for donation
of gametes, to pay for embryos, to pay for surrogacy.
The second major head of activity is what we call the controlled activities.
These are essentially activities that are prohibited unless they
are carried out in accordance with the Act and the regulations created
under the Act. And these activities all require a license that
will be issued by the agency. These are the activities that we
feel are fundamentally acceptable but that we have concerns about
the need for measures to protect the health and safety of people
participating in them. And they are defined in very general terms
which will allow us, in turn, to a great deal of flexibility in
developing the regulations. So the two primary heads are the provisions
allowing us to regulate collection, storage, handling and use of
human reproductive material to create an embryo, and then the storage,
handling and use of an in vitro embryo for any purpose. As well,
there is authority that allows us to authorize the reimbursement
of expenditures of donors and surrogate mothers. Just to note,
both the prohibitions and the controlled activities carry some very
significant penalties as well.
A last key element of the legislation, at least the last I'll
speak to, is that of health information and the council, I know
has identified — or the Commission has identified the importance
of creating good information in this area so that we can make more
informed decisions about the health and safety aspects of this technology.
That is a very — very much something that we hope to be able
to do as a result of the information and privacy provisions in the
Act. The provisions provide — they create a fairly wide authority
to collect, retain, use and disclose health information of people
who are undergoing these procedures and also people who are donors.
They create a privacy framework that is — applies both to
the licensees under the Act for example, the in vitro fertilization
clinics, and also the agency that Mr. Shugart mentioned. The —
precisely because — well because of the sensitivity of the
information and because of the fairly broad scope pertaining to
the collection of the information, this is balanced in the legislation
with a privacy regime that, in fact, is stricter than the general
privacy regime that applies to information in the hands of the Federal
So there's been a balance struck there, a balance which
received favorable comments from the Privacy Commissioner in Canada.
MR. SHUGART: Thank you, Glen. Three points which I think
are particular advances for our country in this area are the creation
of the agency, the information framework that Glen has just talked
about and the comprehensiveness of the approach. The agency is,
of course, modeled to some extent on the United Kingdom model.
It will be independent of the Department of Health, although within
the portfolio of health agencies reporting to the Minister of Health,
no different than what occurs within the domain of several agencies
here reporting to the Secretary of Health and Human Services. It
will be governed by a board that will be broadly representative,
although the appointments to the board are to the person. They
are not formally representative of specific sectors of Canadian
society and it will be led by a chief executive officer to be styled
The agency's mandate is to implement the Act, issue
the licenses, and operate the information registry. The ongoing policy
responsibility remains with the Minister and assisted by the
Department. In fact, it's our view that the Agency will be a home
over time, to the debates that continue related to this field. It is
inevitable that these debates will occur in Parliament as well and in
other parts of society but in a coherent and ongoing way, the agency at
the level of the Board will undoubtedly be a vehicle, a forum, for
transparent and systematic debate about these issues as the field
continues to develop.
It will provide an anchor for debate in what is sometimes a
slippery slope and it will be a focal point for Canadians as that — as
the field evolves. The information framework is, in our view, hugely
important because it provides a view over time of what is actually
going on in the sector. We do not have today any reliable or
comprehensive information about the nature of the activity, the extent
of the activity, the effects of the activity and this information
framework over time will provide us with that.
The comprehensiveness of the package is something that can
be turned to, providing some principles. They may not be universally
accepted but it will provide stability in this sector and ultimately
for the families who benefit from this sector as well as the research
enterprise relevant to it.
Let me focus then, on three challenging issues which we encountered
and which will continue to be, I suspect, hotly debated from time
to time. The first is donor identity. These issues are a challenge
to the proposition that it is only the issue of research relative
to embryos that is bioethically significant and important. The
question of whether offspring should have access to the identity
of their biological parents, that is the donors of sperm or ova,
without the consent of the donor, was key and central to this debate.
Many offspring gave passionate stories about how they felt they
needed this information to understand themselves, their roots, their
identity and this view was strongly supported by many parliamentarians.
Here there was a difficult tension at play. The potential
for injury to the infertile given the serious concern that removing
donor anonymity would deter donations and reduce the supply of gametes,
reducing the chances to have a family through these technologies over
against the legitimacy of the desire of the offspring to understand
their identity. There was a further factor, somewhat technical rooted
in law, given that most provinces had not amended their family law,
which occurs at the level of provinces, to insure that a donor is not
considered the parent in law. As such the provinces were very opposed
to a system of mandatory donor identification without having made the
changes in family law.
In our study of this issue, we found that all countries
that have mandatory donor identification have clarified the legal
status of the donor. With respect to identity, the Canadian
legislation uses a two-key approach. The offspring can request
information about the identity of the donors and the agency will
receive such a request and seek the consent of the donor in a neutral
way, not applying pressure but simply exploring whether the donor would
consent to provide that identity.
The offspring, however, will receive health related
information on the donors. This is part of the information regime that
is established by the legislation. This whole question of donor
identification was resolved in the parliamentary committee studying the
bill by one vote and that carried through into Parliament where the
decision of the committee was retained.
The second issue which, again, is very significant from the
perspective of bioethics is commercialization. This issue was raised
most frequently in the context of sperm donation and of surrogacy. And
again, there were two principles involved. On the one hand, a
principle of the legislation, that is that these procedures and the
human capacity for reproduction ought not to be commercialized and the
pragmatic effect on the other hand of insuring the availability of
reproductive material to provide the basis for building families.
As we mentioned, payment for gametes is now prohibited.
The prohibitions are in effect as a result of the law. However,
concerns over the continued availability of gametes in this environment
of non-commercialization is easily the single most significant issue
heading into the implementation phase. We're in a transition
period right now. Payment is prohibited but the requirement of
receipted expenditures for expenses is not required.
This regime will require Canada to develop an altruistic culture
of donation such as applies now with blood and with organ donation.
We believe that it can be done, but it is going to require work
and effort to bring that culture about and help it to mature. And
I might just note that it is an interesting complexity in the Canada
imports - donated sperm from the United States.
Finally, embryo research; the legislation was considered in
the context of the debate over embryonic stem cell research. However,
the legislation again, to restate what Glen pointed out, applies only
to embryo research in general. It does not cover the broader issue of
research using existing stem cell lines. The legislation prohibits the
creation of embryos for research purposes other than a carefully
constructed provision that allows research to improve IVF treatments
Therapeutic cloning is prohibited in Canada, which is a key
point of contrast, as you know, with the approach in the United
Kingdom. The legislation permits research using IVF embryos created
for reproductive purposes but no longer required for these purposes.
This is only permitted under the operation of a license and that
license will be granted taking into consideration factors such as
evidence of full consent from donors, ethics review through the normal
procedures and the use of the in vitro embryo must be deemed by the
agency to be necessary to the purposes of the research.
These provision cause concern amongst those opposed to
embryo research. Many others thought the legislation was too
restrictive in prohibiting and regulating certain areas of scientific
inquiry. And in our view, it was between those two perspectives
impossible to achieve a compromise that everyone would be satisfied
with. However, we tried in the legislation to clearly set out that
embryo research is unique and requires more oversight than any other
type of research. This will be the only basic research in Canada that
requires a government license. And the continuum of views on the
research involving embryos is well-known. At the one end, this is
really tissue morally indistinct from any other. At the other end that
the embryo is an entity with the full moral status of human life and in
the middle a view that this is an entity with potentiality for full
personhood worthy of special consideration. The middle view was not
proposed by the government as a formal philosophical proposition. This
case about as a result of debate, that is to say that the debate across
that spectrum of views was thorough, was forcefully expressed by
parliamentarians. In the end, this was a combination of legislative
pragmatism, philosophical outlook and an intuition on the part of the
Minister and of the Government and of legislators about what would be
acceptable in the end to the largest number of Canadians.
Now, despite these controversial issues, how did we actually move
to having legislation? Let me mention three aspects. There was
much debate and disagreement about the issue. This was not easy
to resolve in the end but there was more than the intensity of debate,
a consensus that this issue had to be addressed. It was the type
of legislation that no one is 100 percent comfortable with. Probably
every member of Parliament and Senate wanted to change something
but in end there was a strong feeling that we had to start somewhere.
We had to fill a void. Secondly, towards the end of the debate
when it seemed that nothing was going to be certain. Several groups,
women's groups, social advocates, bioethicists and so on, became
even more vocal in support of the legislation even though they were
not 100 percent happy. Their argument was that the real impact
of the bill was to protect the health and safety of women and their
offspring. And it went right back to the origins of the study of
the Royal Commission. They pleaded for decision makers not to lose
sight of the origins of the bill which was that these are technologies
which have enormous potential and they need to come under the scrutiny
of the public's fear and need to be ruled by the public's
The fact that Canada did not have any legislative provision covering
human cloning, particularly reproductive cloning, was a key driving
factor and some developments in the commercial scientific sector
in the United States and an announcement by a group called the Raelians
in 2002 which created a certain amount of public controversy, brought
into relief the void that existed at the time.
We'll conclude with subsequent steps. We made good progress
as I think is evident, but we have not finished this journey by
any means. The legislation, while on the books, in some respects
is only half complete. It requires an extensive set of regulations
to be developed in order to commence the licensing of the procedures
that are controlled and the related research. And this is a major
area of activity in which we are engaged right now through consultation
with the public and with experts.
There is also a clause in the legislation requiring
Parliamentary study of all proposed regulations. We don't
anticipate that there will be that much free time in the day ahead. We
need to establish the agency. We need to recruit the chief executive
officer and the Board of Directors. This will be done again, through a
public process. The legislation provides for a review of the Act three
years following the creation of the agency. This is a clause right in
the law that Parliament will engage in a review of the law. The
purpose of this is to enable Parliamentarians to be up to date with the
latest developments and to satisfy themselves that it still reflects
the public's views on the issue. We're more than happy,
members of the council, to exchange views and provide any further
elaboration. We hope that's been of some use to you.
CHAIRMAN KASS: Thank you very much for a clear and concise
and comprehensive presentation of the essence of what you've done.
The floor is open for questions and discussions and could we have the
lights. It's very hard to converse in the dark. Jim Wilson,
PROF. WILSON: Could you clarify, Ian, for me, one or two provisions?
What led you to ban the purchase or sale of gametes and to rely
instead on a voluntary contribution system akin to the supply of
blood that occurs in some countries, although not in this country?
Isn't that likely to reduce substantially the supply of gametes?
MR. SHUGART: There was concern about that, Professor
Wilson, no question. The prohibition really flowed directly from the
principle that these activities and the materials that are used on the
activities should not be the basis of commercial exchange. That these
are societally important decisions that families make and the view of
the Royal Commission, this was one of the main conclusions that they
came to was that this should not be the subject of commercial
activity. And by extension, the implications were for surrogacy, paid
surrogacy and also for the purchase of gametes or the sale of gametes.
So it really was that simple an extension of that principle.
PROF. WILSON: Well, since I don't understand the
objection to commercialization, and please forgive me if I press a bit
more on this, extracting sperm is not an especially difficult matter.
Extracting an egg is a difficult matter and to not pay women for the
sometimes burdensome procedure involved, it seems to me restricts
substantially the supply of eggs for those persons for whom an egg
should happen to be necessary. But the argument against
commercialization in your view covers that ban without exception.
MR. SHUGART: Well, it is what underlies the ban and there's
no question that that was the tension the Parliamentarians faced
and it, in fact, is one of the reasons why Parliament said, "We
want to — we want to look at this law again. We want to see
what the effect is". We will, through the information, the
reporting requirements, be able to know over time what the effect
is, the supply of gametes and as we mentioned, there's no question
that the development of a culture of altruistic donation which applies
in some other countries and has been developed, is going to require
some focus and some work.
Whether in that area the law will absolutely remain the
same, I can't predict, but in our Parliament, there was a very
strong view that this was as important a principle as virtually any
other within the scope of the bill.
PROF. WILSON: If I could just pursue this one more moment,
you do not wish sex selection to be engaged in for anything other than
correcting a sex related disorder. So that a family that has four
girls and would very much like a boy, this cannot be done under
Canadian law by using some PGD procedure increase the odds you're
selecting a male sperm.
MR. SHUGART: That's correct.
PROF. WILSON: But that can be done in the United States,
so should we open up another flight from Canadian Airlines to Chicago
to accommodate the customers?
MR. SHUGART: Well, we rejected any notion of
extraterritoriality, so all we could do was put in place the regime
that reflected a Canadian perspective but it is absolutely true that
there is an open border between our countries.
CHAIRMAN KASS: We can also fly to Hong Kong and take advantage
of the, you know, nice Chinese offer. I understand. And a tiny
point in this, Mike Gazzaniga wants the floor in a moment, but just
to clarify, one of the ways in which American fertility clinics
are dealing with this question of the supply of donated materials
is to provide reduced costs to the first couple if they are willing
to make their surplus embryos available to other couples. That's
not exactly the buying and selling — I mean, you could say
that's not exactly the buying and selling of the materials but
the question is, does your law deal with that and would that be
— would that be a way around this that's acceptable in
Canada or not?
MR. RIVARD: That practice has been known in Canada and it
is caught by the prohibition.
CHAIRMAN KASS: I'm sorry?
MR. RIVARD: It is prohibited. It is part of the
prohibition. So the purchase of gametes includes exchange for
services, for example, any exchange of value.
CHAIRMAN KASS: Now, let me repeat. If a couple comes to
an in vitro clinic and says, "We're prepared to allow the
surplus embryos to be donated" and the doctor says, "In that
case, we will give you a reduced rate for the services here",
that is explicitly covered by this prohibition?
MR. RIVARD: I think what would be caught in the
prohibition would be the second part of that phrase, in that case
you'd benefit from a reduced rate.
CHAIRMAN KASS: Okay.
MR. RIVARD: The donation of the surplus embryos is by no
CHAIRMAN KASS: Not a problem. Clear. Michael Gazzaniga.
DR. GAZZANIGA: I'm curious in the history of the debate
that led up to the legislation, the way it's structured now
is the stem cells harvested from leftover IVF embryos can go forward
under licensing; whereas, there is absolutely no capacity to use
therapeutic or biomedical cloning to reap stem cells. We've
been through these moral arguments on that point and a lot of people
have trouble distinguishing those two cases. How did the discussion
go in Canada and when it finally came down to whether this bill
was going to go forward or not, did it turn out to be a vote that
some people simply rejected the view and some didn't and could
you have predicted it by what people believed in their personal
MR. SHUGART: I would say a couple of things on that.
First of all, I think that the starting point of the debate was
influential in this sense. The government in our system for the most
part proposes to the legislature a piece of legislation. It is not
built from the ground up to the same extent as perhaps the
congressional system could be described as doing. So that the decision
of the Minister and of Cabinet in coming down on some of the key
provisions was important as a starting point for the debate.
Of course, the full range of views was expressed by
individual Parliamentarians. It would seem in retrospect that the
Minister and the Cabinet had predicted with some accuracy and reflected
with some consistency the views of a majority of Parliamentarians. So
that while there were opposing views on whether the creation of embryos
for research purposes should be allowed, in the end that was supported
by a clear majority of Parliamentarians.
I understand that objection that fundamentally there is no
distinction in terms of the moral status of an embryo, regardless of
its purpose in coming into being. That does seem, however, to be a
point of gradation along that spectrum of views, that purpose is an
important factor in bioethics. And that the existence of supernumerary
embryos as a result of another purpose is capable of differentiation
from a different purpose which is to produce an embryo for research for
therapeutic purposes. I fully appreciate that that distinction is not
accepted by everyone but I think in the range of views, it is a
qualitatively different point on the spectrum.
We did not, as civil servants, really engage in any
predictive exercise on the basis of members of Parliament, although as
we interacted with them, the views of different Parliamentarians became
clear. We advised and implemented the views of Ministers and the
Government and did our best then with Parliamentarians to provide
explanation and awaited the outcome along with everyone else.
CHAIRMAN KASS: Gil Meilaender?
PROF. MEILAENDER: In our discussion yesterday afternoon,
Paul McHugh expressed, if I'm — if my memory is serving me all
right, a certain kind of skepticism with respect to the surplus embryo
question, the kind of skepticism that one might express by saying,
"Well, if we're going to allow those surplus embryos to be
used for research, the IVF industry will indeed produce plenty of
them. So that technically they're produced for reproductive
purposes but in fact, that's not quite what's going on. Did
that sort of issue get raised and discussed at all? Is it deemed sort
of an overly suspicious and too skeptical kind of view? Did it just —
did it not make its way into the debate at all? I'm just curious
to know whether it even came up and was considered.
MR. SHUGART: Well, Professor Meilaender, I'm trained
to be skeptical but not suspicious. But indeed it did come up and one
of the provisions in the regulations again, driven by Health and
Safety, is to — or will be to put limits on the number of embryos that
can be produced from a particular cycle. The purpose of that will
indeed be to address the health concerns of the subject of the
procedure. The effect of it may well be to provide a check on the
phenomenon of deliberate over-supply of embryos.
CHAIRMAN KASS: Please.
MR. VANDERGRIFT: If I could just mention something, two
other factors that were prominent during the debate, one driven by news
media reports of various developments, one dealt with the issue of ova
freezing and to the extent to which that might be the solution to this
question. And members of Parliament accepted that the science may not
be there yet but I think one could anticipate that there will be a
watching brief on developments in that field as the regulatory
framework moves forward.
The second was discussion about the relationship between
investigators or researchers and clinics themselves and what might be
— how that relationship might be sorted out, for example, in the
question of who can obtain informed consent, for example. So I think
this speaks to what Parliamentarians felt as being the importance of
having an overall regulatory framework because it provides tools to get
at some of these issues as they develop.
MR. RIVARD: If I can add just a point on that, too, I would
be a little more concerned about that if the — if we had simply
adopted prohibitions in the absence of a governing framework for
say the IVF clinics. These clinics, therefore, they will all have
to be licensed. They will be subject to government inspection and
a fair degree of control and insight into their operations. So
while it's always possible for somebody to try to evade the
law, it's — there's certainly not — they will
not be operating in a vacuum. They will be subject to a fairly
tight regulatory and inspection regime.
CHAIRMAN KASS: Paul McHugh.
DR. McHUGH: Well, I celebrate this enterprise of our Canadian
friends and I think that it will accomplish just want I certainly
look forward to hear by having a forum where coherent discussions,
as well as overall regulations that can be altered, changed and
developed over time by thoughtful citizens. And therefore, I was
very pleased by this wonderful presentation you gave us. I did
just — this is just a simple question tied to this, and that
was, first, this interim voluntary moratorium on non-applications
of reproductive technologies in 1995, did that moratorium cease?
MR. SHUGART: As a result of the coming into force of the
prohibitions in the bill, yes.
DR. McHUGH: So it ceased in 2004.
MR. SHUGART: Yeah.
DR. McHUGH: So it went from 1995 to 2004.
MR. SHUGART: Uh-huh.
DR. McHUGH: And that moratorium was —
MR. SHUGART: As far as we can tell —
DR. McHUGH: Uh-huh, uh-huh.
MR. SHUGART: — in the absence of any reliable information
to know for certain.
DR. McHUGH: Right, but government supports were not given
to that kind of enterprise in research during that time.
MR. SHUGART: No.
DR. McHUGH: And the other thing is, we have had a
presentation here by a person who was the representative of groups of
people who had anonymous donations in their conception and she made a
heartfelt plea for the idea that this was a practice, this anonymity
was a practice that caused considerable suffering on their part. And
given what you've put here in place and given that there will, if
this is the case, be more and more of these people, presumably your
enterprise will be the forum for these people to re-plea their case,
will it, or will it go back to Parliament where one vote swung the
MR. SHUGART: In terms of any change in the legislative and
regulatory framework, then Parliament would have to decide but the
issue will no doubt be debated in the forum. I have absolutely no
doubt whatsoever that the Board will be able to advise the Minister of
Health and the Government on regulatory change over time and therefore,
it is by no means irrelevant or secondary to that issue but again, the
potential in the individual case for the link to be made
notwithstanding the law supports anonymity, the individual may well
appeal to the agency to approach the donor and if that exchange is
successful in that case, then there is every possibility of the donor
consenting to the information, the identity being released but it's
a regime that requires the informed consent of the donor to give that
So in the individual case, there is no reason to believe
that identity will always be anonymous.
DR. McHUGH: Yes, that's very interesting. By the way,
does the same apply to adoptions? Is similar anonymity, informed
consent still applied to adoptions — adoptees who later in life wish
to know their parental origins?
MR. RIVARD: That is generally speaking the rule in
Canada. I think historically there was a pure system of anonymity.
Increasingly jurisdictions are moving to a situation where they have
the records that allow an individual to make a request to find their
biological parent's identity and then can provide that with
consent. So it's somewhat parallel.
DR. McHUGH: So once again, it's in parallel. The
biological parent also has the option of saying no.
MR. RIVARD: That's correct, yeah.
MR. SHUGART: And that is governed by provincial law not
CHAIRMAN KASS: Mary Ann Glendon.
PROF. GLENDON: I'm wondering if you could say a
little bit more about informed consent. How detailed would you expect
the regulation to be? For example, would the clinics be required to
give women information about the success rate, the health risks to the
woman, information such as it is that we have concerning possible
health risks to any children that might be brought into being through
MR. RIVARD: First, I would say that the concept of informed consent
in Canadian law is very similar, if not identical, to American law.
All the fundamental principles are the same. The — and the
legislation expressly incorporates that common law and applicable
provincial statutes into the legislation. It's also foreseen,
however, in the legislation that specific information requirements
will be set out in the regulations and therefore, for example, if
you are a woman going to an IVF clinic, that clinic will have to
provide the information that the regulations require. We haven't
yet reached the stage of defining what that data will be and we
haven't yet consulted on that also but certainly those are all
issues that I think would be addressed in that process.
MR. VANDERGRIFT: If I might, this was an issue that came
up during the parliamentary proceedings and, in fact, a member of
Parliament succeeded in amending the bill to add a provision that
regulate — the clinics in this case must provide to prospective
patients information on success rates so that was actually specified in
the legislation and the rest will be spelled out in further regulation.
CHAIRMAN KASS: I have a series of things and I don't know
whether you prefer I do them one by one or whether you — why
don't I start and then you can — if there's too much
we'll — you can just interrupt me. I, and I think not
only I, am interested in how what you've done differs from what
the British have done and also how it relates to what might be done
here. So let me begin with an observation or comment and see whether
you think this is correct and what might account for it. If you
look simply at the prohibitions or at the things being regulated,
the difference between this and the British system seems small in
some ways. You could sort of point to cloning for biomedical research
prohibition as perhaps the major difference but if you look at the
overall — at the overall package, a number of things strike
me as being very different.
First of all, in the way that domain in the scope and its
definition, even in the very name of the Act is different. I mean, to
talk about fertilization and embryological authorities as opposed to
assisted human reproduction or — you seem to have taken a broader view
and the question is not what do you do with embryos, but how do we
think about human reproduction given these new assistances.
Second, the list of the principles strike me as different. I
don't have the HFEA Act firmly in mind but I would be surprised
if the language, among other things, of protecting human dignity
occurs in that context, and finally, the origins of this, if we
allow the Royal Commission to be part of the history of this story,
suggests that this is not to begin with — well, this may be
somewhat unfair to the Brits but that was undertaken with, I think,
not only the participation of, but I think probably at the instigation
of, the scientific community, that saw that unless they got something
like this in place, that there would be hell to pay and the research
couldn't go forward and in some ways that is a research facilitation
act, whereas this looks to be something which comes from the public
at large and is not somehow driven from inside the community; that
has some bearing on the question of what enabled you to succeed
and what might prevent us from succeeding here. So I wonder if
you'd first comment on whether those perceptions are accurate
and what difference it might make.
A second question has to do with how it was that you were able
to effect this kind of compromise. I mean, you did indicate in
the slides, and they impressed me, as to what the key factors were
that enabled you to move this forward. And one additional thing
might be to ask, I mean, is it the case that you don't have
the kind of polarization that's been caused here by the Roe
v. Wade decision as the kind of political background and that
somehow made life a little easier for you? Why is it that you didn't
have an aggressive sort of scientific community lobbying against
this, and is it that the lobbying practices in Canada are different
from what they are here? How was it that you were able to get people
who might be very powerfully unhappy either with certain prohibitions
or with certain permissions to say, "Okay, this is the best
that we can do"? Because that isn't the spirit that has
governed these discussions in this country at least not to the present
time and especially if Frank's proposal comes in with his dukes
up, he is unlikely to succeed in the current Congress for the foreseeable
MR. SHUGART: Could I stop you there?
CHAIRMAN KASS: Please.
MR. SHUGART: Please, sir, may I leave the room, my brain is
full? I'll respond to those and invite my colleagues to join
in. The difference with the UK and prospects for the United States,
I will sidestep that question precisely as you put it, particularly
anything predictive about the United States. I would make a couple
of observations. I think in retrospect it would be difficult to
overstate the importance of the fundamental purpose of the legislation
being to address health and safety issues. I think that provided
the debate about the ethical principles, certainly not to disappear,
not to be diminished in their importance, but put in the company
of principles and purposes that were, in their own right, profoundly
important. In other words, constraining these technologies and
the use of these technologies in the interest of couples, of women
in particular, and of children in particular.
I think that there's no question that that had a
salutary benefit on the whole public discussion, including
consideration of the ethical principles. And there as a trail of
purpose, there was a clear public record, outlining that was the kind
of issue that was driving this discussion.
Secondly, the government was confronted on occasion with
suggestions to split the bill and hive off the issue of cloning from
the regulatory dimensions. In other words, makes some prohibitions
about human cloning. The government held fast on the holistic view
that these issues needed to be addressed as a piece. There were, in
fact, implications of the prohibitions for the controlled activities
and the need for regulations. And that if one split the bill, that
would potentially lose the grounds on which one could develop a
regulatory approach and would put at considerable jeopardy the
prospects of ever returning to the health and safety considerations
which were hugely responsible for initiating the discussion in the
And secondly, there was prime facie, no reason to believe
that splitting the bill would provide a peaceful resolution of issues
in regard to cloning, for example. So it was very important that the
government held to that proposition. And it was able to do so largely
because of the time in question, the government of the day commanded a
majority in the House of Commons. At the moment, that is not the case.
Thirdly, with respect to researchers, I'm not a
sociologist, I'm not a scientific sociologist, I don't know the
extent to which different views among and of researchers would compare
with the United States. It is a continental if not global fellowship,
of course, but it may have something to do with the nature of public
discourse in our two countries. I did say that as a general rule of
thumb take what happens in Canada and multiply it by 10. It may be
that that principle could apply to intensity of public debate as well.
But it was very important that the positioning of
scientists themselves was supportive overwhelmingly supportive of the
approach that the government was taking. Scientists in Canada in this
field and in related fields, were saying we need a regulatory regime.
Self-regulation in this domain is not in the long run appropriate and
so at no point did the government find itself face-to-face, toe-to-toe
with the research community. On specific points, yes, of course, there
was variation of views within that community and there were some who
took the view that the criminal law was an utterly inappropriate way of
dealing with this whole field.
It was important to make the distinction between a
jurisdictional head of power and a law that would be written to
criminalize certain kinds of activity but again, the government took
the view that some provisions of this bill were enormously important
for the nature of human life and of reproduction and of society and if
the criminal head of power was not appropriate for some of these
issues, where was it appropriate.
But in the main, there was a strong view from researchers that
this was — this regulatory framework was a necessary thing
to do. With respect to the issue of polarized debate, I have a
hunch that while it was awkward and difficult at times, the serialization
of this debate over a number of years may actually in the end have
been helpful in achieving some resolution because it gave a profile
to some of the issues and time for views to mature, time for exchange
to occur and ultimately in Parliament there was a recognition that
it was time to move. The requirement that the government table
with the committee the regulations that were proposed and the Parliamentary
review that is built into the legislation where I think safety valves
as well that allowed ultimately a decision to go ahead, it reduced
somewhat the enormity of the stakes as some would have viewed them.
I think all of those are factors. I don't know, colleagues,
if I've left out anything serious?
MR. RIVARD: I guess I would just add, too, that the —
really the primordial issue was the question of legislation versus no
legislation. I mean, that was the reality in Canada. There was no
legislation in this area. And so you know, at some point everyone who
had some issue or some question with the bill, had to face that reality
and there's sufficient consensus developed that, although not
perfect in anyone's eyes, this was a much better state of affairs
than what existed.
MR. VANDERGRIFT: I would also just quickly add that I
think one could easily anticipate a very vigorous three-year review
of the act as a number of issues that people accepted for the time
being will definitely, I think, come back on the table again at
that point in time. So I think, the depiction of that as a safety
valve, I think was quite accurate.
CHAIRMAN KASS: If I might, I have two more. One is the
question of the importance of gathering the information and the
issue of privacy. This is a difficult problem here. And in fact,
one of the arguments against doing longitudinal studies for outcomes,
one of the reasons we haven't had it is the patient groups are
— zealously guard the privacy of the information and our own
recommendations in the Reproduction And Responsibility report that
we should in fact, have supported longitudinal studies — until
we got in there, the participation should be voluntary, et cetera,
et cetera — we were really very much badgered on this question.
And we also have the Privacy Act, what's the technical —
the HIPAA Act, which gets in the way of — I believe we were
talking about this yesterday — gets in the way of getting
all kinds of indispensable information out.
So if you could say something about how you have managed to steer
the course to get the kind of information — outcomes information
that you need while dealing with this privacy question, that might
be useful to us. And then finally, something on the composition,
the idea for the composition of the — of the regulatory body
itself, not only membership but to — refer to a question that
came up in Frank's presentation yesterday, how do they conceive
of their task? Are they merely the enforcers of the norms tacitly
set by Parliament, or have you indicated that this really is going
to be the place where this debate is going to take place and they're
going to be making some decisions probably on new developments that
the Parliament hasn't had an opportunity even to anticipate?
Are these going to be the followers of public opinion, the
shapers of public opinion, the conscience of Canada? I mean, what sort
of — the anticipated spirit of their activity and what kind of idea
for their composition governs, I don't mean the particular members,
but what's the idea of who these people should be ideally?
MR. SHUGART: With respect to the information and privacy,
I think a number of — I'll ask Glen to comment briefly in this
area as well, but I think that the regulations will need to pass the
standard that the information sought through that regulatory authority
would be appropriate for the public policy purposes behind it. In
other words, it's not simply enabling the gratuitous collection of
information. There needs to be — there needs to be purpose. The
privacy regime and the regulations need to deal with the issue of the
use and disposition of that information, in other words, provide the
safeguards against inappropriate use.
Clearly, the centerpiece of the information requirements is the
medical information that may be particularly germane to the offspring
as well as information relevant to procedures themselves which over
time would be important baseline information for enhancing the safety
of those and efficaciousness of those procedures. This is an area
where we have the interface of the individual clinical experience
and the public health requirements of information where conceptually
the way of dealing with those two things is inherently different.
In public health, typically information is only useful to the extent
that information collected individually is aggregated for the benefit
of more than the individual who provided the information. So there's
an important balance here in terms of the purposes for which the
information is collected and the safeguard is the management of
that information once collected. Glen, is there anything that you
think we should add to that and then I'll address your second
question, Dr. Kass?
MR. RIVARD: Well, I just would add that there are
provisions that will allow for the collection of information up front
if you will, that is prior to donation, prior to participation in a
regulated procedure like IVF. But if by longitudinal studies you mean
the ongoing following of the mother and even more particularly the
offspring, that will require voluntary participation and the department
will have to develop strategies to do that sort of research.
The — I'm familiar with HIPAA. There's similar legislation
in Canada. What we did in effect under this act was, we created
a privacy regime specific to the collection and the use of the information
under this Act. Now, our starting point was compliance with generally
accepted privacy principles and we made this as congruent as we
could conceivably with existing privacy legislation. As I indicated,
there are some fairly broad provisions up front for collection of
information that's balanced by actually a more restrictive regime
governing the disclosure of that information than is generally applicable.
And that received the endorsement of our privacy
commissioners, so that's how we dealt with that particular
MR. SHUGART: With respect to the Board, I'll answer a
question you didn't ask if I may. It's germane to your
question, however, and that is the provision in the legislation fairly
strong provisions, I would argue, with respect to conflict of interest
of board members. Licensee's, for example, may not serve on the
board. As one reflection of guarding against conflict of interest. Of
course, there was a discussion about the nature of the board, whether
or not to have a board in the first instance. Once that was resolved,
what should be the basis upon selection of board members, what's
the overall character of the board and it was decided that the board
should not simply be a vehicle for resolving differences of interest or
of view. In that sense there is an echo of yesterday afternoon's
discussion with respect to the history good and/or bad of commissions
versus other regulatory bodies styled somewhat differently.
The selection of members of the board will undoubtedly in
the end reflect a diversity of views and of interests but the basis
upon which board members are selected is individual and not
representativeness of a particular view and that is deliberate. We do
believe that while the board is charged with the oversight of the
agency, it therefore, has an element of good governance practice about
it, quite apart from everything else. The — it also does serve as a
forum for discussion and debate. I would anticipate without prejudging
anything, for example, that the board will have a series of vehicles
for informing itself and the public thereby, of developments in the
field, and the issues that are — seem to arise as a result of those
developments. It will advise the government but the legislation is
quite clear that the policy responsibility rests with the Department of
Health so as to constrain the ability of the agency simply to define
its own future absent broader considerations of public policy and so
on. So that, itself, is a careful balance.
There have been different attempts to characterize it as
quasi-judicial, purely a forum for debate and so on. It's
difficult to imagine after a period of what might in the end be
somewhat more organic development exactly how it will come out, but
those constraints are there. One interesting point to observe is that
the — in the granting of licenses, that task cannot be delegated to
staff of the agency. Granting of licenses must be done by members of
the Board so they do have an important administrative and decision
making role which makes them more than just a collection of interest
There was a debate about whether scientists should be eligible
to serve on the board because "everyone knows what their view
will be." It was resolved in the end that this should be
an informed board and that exclusion of scientists from the board
would not serve that objective. So as you can tell, the discussion
was actually quite varied and extensive. The goal in the end was
to provide oversight, ensure that — given the societal sensitivities
and importance of these issues — that a group visibly charged
with oversight in this area should have that responsibility and
actually in very real terms carry it out, but that it should not
be a vehicle for resolution of narrow interests.
CHAIRMAN KASS: Thank you very much. We've come up to
the time for the break. I want to thank Ian Shugart and his colleagues
for a really very clear, forthcoming and very helpful presentation. We
have a very full next session, so let's be back at 10:15 and we
will start then promptly. Thank you very much.
(A brief recess was taken.)
SESSION 6: SEEKING MORALLY
UNPROBLEMATIC SOURCES OF HUMAN EMBRYONIC STEM CELLS
CHAIRMAN KASS: In this last session before
the session for public comment, the council returns to the subject
of embryonic stem cell research, not to continue to argue about
the moral issues or to discuss the wisdom of the current federal
funding policy, but to explore two very interesting proposals demanding
public attention that suggest means of deriving embryonic stem cells
that would get around the morally charged necessity of doing so
This council, I think, has distinguished itself in the discussion
of these questions, notwithstanding our sharp differences of opinion
about the conclusion, in recognizing that all parties to the existing
debate, in fact, have something vital to defend — not just
for themselves, but for all of us. We have recognized the importance
of the scientific research and the medical benefits to which it
will lead. We recognize the supreme and important value of respecting
human life, indeed in all of its stages. People may differ about
how much respect and at which stage, but these are important human
goods and it would be very exciting if ways could be found in which
these two goods did not have to be pitted against one another, but,
in fact, could be embraced by all people whichever way they pitch
the balance amongst them. And therefore it's, I think, of great
interest to this council that we have for presentation today two
such proposals: one presented by Howard Zucker and Don Landry, both
from the College of Physicians and Surgeons at Columbia University,
Howard Zucker from the Department of Pediatrics, Don Landry from
the Department of Medicine. And their proposal, which we will have
had occasion to read, talks about the possibility of deriving human
embryonic stem cells from no-longer-living, not merely just non-viable,
not merely doomed-to-destruction, but actually no-longer-living
embryos. And our own colleague, Bill Hurlbut, has a proposal for
deriving — that would enable people to derive human embryonic
stem cells from embryoid-like bodie,s but which are not in the strict
sense embryos proper. We look forward to the presentations.
I should say, so that there won't be any misunderstanding,
these are not at the moment presented as council proposals. The
council is simply eager to hear about this and we will see in the
discussion afterwards what council members think about these things.
But first, we have to inform ourselves about them both with respect
for the question of the ethical issues and of the scientific feasibilities.
So Howard Zucker and Don Landry, welcome to you and the floor is
first yours and then we'll proceed to Bill.
DR. ZUCKER: Thank you, Dr. Kass, and Don and I would like
to thank the entire Bioethics Council for giving us the opportunity
to present before this illustrious panel. We recognize that the
stem cell controversy has resulted in a very polarized and heated
debate but it is our personal opinions that there is a common ground
for medicine, for law, science, and ethics that can be reached,
and we published this view in the Journal of Clinical Investigation
last month which you all have a copy of.
Scientists cannot go anywhere without a laptop and visuals and
so, in the interest of efficiency, Don will present our paper, after
which we will be happy to answer any questions that you have for
us, thank you.
DR. LANDRY: I also thank you for the opportunity to present
our ideas to you. Let me say also that I'm Director of the
Division of Experimental Therapeutics in the Department of Medicine
at Columbia. I don't engage in stem cell research, so I don't
have a vested interest in this beyond that of a concerned citizen.
I do take care of critically ill patients in a small private practice
and I think it's the context of seeing death in a close and
personal way and seeing the issues of organ donation that informs
to some extent the ideas we're going to present today.
I'm going to present some things that are painfully obvious
to you but I think are important just to state the premises upon
which the proposal was based. The creation of human embryonic stem
cells involves the destruction of an embryo, well known to you.
What that means to an individual depends on how they answer certain
questions. When it's formulated in the most general sense,
when does life begin, it doesn't make very much sense to me
but these are my answers to these questions. Life begins two billion
years ago, human life begins 200,000 years ago. A new human life,
a new human being, a genetically unique entity begins at conception.
A human person, however, is not a question — the origin of
a human person is not a question that science alone can answer.
And so this tension between human being and human person results
in a conflict. We have on the one hand a requirement for respect,
for human dignity, to treat humans as subjects and not objects,
pitted against the drive to relieve human suffering.
And there is no easy compromise. This is not an economic matter.
The differences cannot be split. And so between, on the one hand,
persuasion, which is difficult to achieve, and imposition of will,
which is unseemly, there's a third way, a search for a common
ground, which I think is one of the central activities of this committee.
Our general notion is that death is such a common ground because
the death of the human being subsumes the death of the human person
and so whatever the disagreements about the origin of a new person,
with the death of a new human being that issue of person is also
Some background from the death of a developed human person can inform
our thoughts on the death of the developing human person, and so
just a quick review of some recent history and our notions of death
for developed individuals. Prior to the 1960s going back for thousands
of years, irreversible cessation of cardiopulmonary function was
the definition of death and improvement in respiratory technology
led to a crisis. It was possible to maintain ostensibly dead individuals
for extended periods of time and this crisis was addressed by an
ad hoc committee of the Harvard Medical School with a definition
of irreversible coma that becomes the basis of our modern notion
of brain death.
And in that context of a definition of brain death, not driven by it
but in the context of it, cadaveric organ donation went from speculation
to standard of care and so I would abstract from this slide the
idea that the availability of material, if obtained in an ethically
reasonable fashion, can actually drive research and drive progress.
Some comments also about the legal definition of death. First
of all, it's a specific question of fact, not a question of
law, and so it's determined by physicians. And yet there are
legislative attempts to codify it. Originally, there were two separate
definitions of death contingent on the desire to harvest organs,
clearly a problematic issue. This was resolved by Capron and Kass
in 1972 articulating a single concept of death, but application
of a particular criterion would depend on the circumstances, the
circumstances of machinery maintaining a dead individual that makes
the application of one or another criteria particularly difficult
or facile. A variety of laws follow, tend not to precede some consensus
on the issue and we conclude with the Omnibus Reconciliation Act
of 1986 that, at brain death, the removal of vital organs for transplant
is legally and ethically permitted.
We have criteria for brain death. Our notion is an irreversible action
critical in brain stem function that gets translated through observational
studies, when does someone no longer wake up, finally to diagnostic
tests, unresponsiveness to pain, inability to breathe off ventilators,
certain eye movements upon putting cold water in the ear canal,
a flat EG and the absence of conditions that might otherwise suppress
Embedded in all of this is the concept of organismic death, the
human — the adult or developed human that has died is not
thoroughly dead. Organs are alive, they're available for transplant.
The tissues that make up those organs, the cells that make up those
tissues are alive, and so we like to extend this idea to the developing
human. The developing human, just as for the developed human, is
more than the sum of the lives of constituent cells, and so just
as the nervous system integrates tissues and organs in the developed
human, so too there's a system of chemical communication and
surface recognition that integrates cells in the developing human.
Deprived of the necessary internal signals, an irreversible arrested
cell division can occur.
Our specific proposal, then, is a new definition of death for
the human organism, an organism in development, and that is the
irreversible arrest of cell division.
Now, what are the prospects for producing normal cells from dead
embryos? Just as a backdrop to this consideration, consider for
a moment that 60 percent of IVF embryos fail to meet criteria for
viability. Non-viability is one of those vague terms. It's
an incapacity to develop to live birth and so it contains a number
of categories embedded in it, but there is a morphologic criterion,
abnormal appearances of one sort or another, also a functional criterion,
failure to cleave at 24 hours. Important to note, non-viability
does not mean dead but the functional criterion, cleavage arrest,
likely correlates. Now, cleavage arrest most often reflects various
genetic abnormalities and this might seem to eliminate any prospect
for some useful development occurring from these considerations,
not that the considerations are invalid but that nothing good would
come of them.
But there are several studies, two that I include in the binder,
and summarize very briefly here, that suggest some prospect for
producing normal cells from dead embryos. So Laverge et al observed
mosaicism and, briefly, from 166 frozen embryos that were thawed,
78 remained arrested at 24 hours, 71, no further sign of cleavage
at 48 hours, and fluorescence in situ hybridization, which allowed
examinations of chromosomes X, Y and 1, on all blastomeres of 63
arrested embryos, was performed. Eighty percent showed chromosomal
abnormalities. Aneuploidy, severe aneuploidy was common but mosaics
were present with normal diploid blastomeres embedded in this sea
of abnormality. Voullaire et al also observed mosaicism, 63 blastomeres
from 12 unselected embryos thawed after five years of cryopreservation,
two out of 12 were in cleavage arrest, partial arrest was observed
In this case, they used comparative genomic hybridization,
a powerful technique that's able to look at all chromosomes with
the exception of several that overlap, 17, 19, 20, 22. Again, they
noted marked aneuploidy, very common but also the eggs were identified
PROF. WILSON: Excuse me.
DR. LANDRY: — with no diploid blastomeres in five of 12
PROF. WILSON: Could you define aneuploidy, please?
DR. LANDRY: Aneuploidy is multiple copies of chromosomes,
and so, instead of the normal diploid, we can have tetra and beyond,
sometimes five full sets of chromosomes, and this is a marked abnormality
that does not bode well.
Now, if one could obtain live cells from dead embryos, are
they truly normal, what is their developmental potential? I've
presented human data till now. This is the one bit of animal data that
I'm going to mention but it's so marked that — and
understanding limitations in animal data, it's still worth
mentioning here. In one experiment, cloned tadpole embryos showed 99
percent irreversible arrest, 95 percent early on, 99 percent overall.
Now, cells from arrested blastocysts were aggregated and an individual
cell is injected into a normal tadpole blastocyst. Twenty-five
percent resumed division and were stably incorporated into differentiated
tissues, becoming muscle, for example. And so blastomeres from
an arrested embryo can be reprogrammed for differentiation and growth
if placed in the proper environment. And this is a natural environment,
but in principle it could be an artificial environment made up of
cell surface proteins and various chemical mediators.
Back to human data, an experiment by Alikani and Willadsen, 107
"non-viable" human IVF embryos were disaggregated. Two
hundred forty-seven intact cells were isolated and they were combined
in 36 aggregates, approximately six to seven cells per aggregate.
Thirty-three percent of these went on to develop and form normally
organized blastocysts with defined inner cell masses, again indicating
that a new environment can re-establish growth and development.
So a summary; we're proposing a new definition for human death,
irreversible arrest of cell division. The criteria for determining
irreversibility would begin with the natural history study of cleavage
arrest and progress to biochemical markers for irreversibility.
Many embryos generated for IVF are organismically dead. Aneuploidy
is present but, due to mosaicism, normal cells are found and it's
at least arguable that they could have normal developmental potential.
The signals required for transforming blastomeres into stem cells
without recourse to the formation and destruction of human blastocysts
is an area of current research. Interest in this area would increase
markedly if, in fact, there were material to pursue this work.
And we propose an ethical framework for investigating embryonic
cells from organismically dead embryos, and this framework would
parallel the cadaveric donation of central organs with consent of
next of kin, in particular organs donated from children with the
consent of parents.
So, in conclusion, application of the ethical framework for central
organ donation to the harvesting of human embryonic cells from organismically
dead embryos maintains respect for human dignity and can advance
biomedical research. Now, two corollaries that do not appear in
the paper but I would be interesting in hearing your thoughts on:
with a clear and clean recognition of embryonic death also comes
the recognition of embryonic life in extremis. And one can apply
the ethical norms for research on a patient in extremis, which are
different from the average patient, to the embryo in extremis.
And so, for example, the extraction of a single blastomere from
an embryo in extremis would not seem to be an enterprise that would
have severe ethical or moral problems. And I've engaged in
research on adults in extremis with the approval of our IRB, engaging
in interventions that would not be permissible with someone not
in the last few hours of life.
This is not an idle consideration with respect to the embryo.
Consider on the one hand organs harvested from an executed prisoner,
mesenchyme from an aborted fetus, versus cells obtained from an
IVF embryo that died despite best efforts for its life. It would
seem that there's a very bright line separating these. What
if cells from a cryo-preserved embryo that is thawed after five
years of storage and allowed to succumb, some may feel this is all
right, some may feel it's problematic but certainly an embryo
in that position is in extremis, and harvesting a single cell a
potential risk but not a lethal, unnecessarily lethal event, might
be considered morally acceptable. And that concludes my remarks,
and Howard and I are available to answer questions as best we can.
CHAIRMAN KASS: I think that — let me suggest that we
discuss each of the presentations briefly rather than have them both
together and to raise any kind of technical question. The presentation
was luminously clear as is the paper. I mean, I think everybody
understands what this is about, so there might be people who have
either technical questions about the scientific feasibility or what we
might know about the likelihood of this, but let's take at least a
few minutes to make sure that everybody understands what they need to
and get ideas clarified. Then we'll have Bill's presentation
and then we can discuss the two things together. So the floor is open
to Doctors Landry and Zucker.
Now, Paul McHugh?
DR. McHUGH: Just one question; you told us you could take
a cell out of an embryo that you had demonstrated aneuploidy in the
embryo and then those cells would reproduce when placed — this, I
guess, was the tadpole work. Aneuploidy cells can reproduce and they
produce cancer. How will we be sure that this method won't
technically lead to the implantation and the use of cells that will
have cancerous potential?
DR. LANDRY: You can simply screen for that. The cells you
isolate, you know, are grown. You can take one of those cells having
now grown and analyze it, so I don't think there would be any risk
of cancer in that circumstance.
DR. McHUGH: Even after you've transplanted them?
I just need to understand the technology a little bit. You have
this embryo. You say you find aneuploidy in it in various cells.
You find 33 percent of them will grow later in the tadpole. Were
those 33 percent of cells you grew in the tadpole demonstrated to
lack aneuploidy in every one of them?
DR. LANDRY: No, and remember that we're not suggesting that
this be used for reproductive purposes. This is meant for in vitro
use and as such, while it's always possible that there could
be unforeseen events, one gets to observe these cells for extended
periods of time. I mean, after all, the ultimate objective of stem
cells, stem cells are indefinitely reproducing ideally by definition,
and so it's possible to go and at any point now having produced
this cell, to examine it and one would seek to eliminate, for instance
abnormalities such as marked aneuploidy and —
DR. McHUGH: Let me just continue on this because I just want
to be sure I've got it. And sticking with the tadpole experiment,
the cells that were later put into the tadpole from frog embryos
that were known to be non-viable for a variety of reasons including
aneuploidy, that those cells had gone through a sufficient phase
themselves to know that they did not carry an aneuploidy potential
and a cancer potential.
DR. LANDRY: The experiment on tadpoles involved arrested
embryos. They were not examined for aneuploidy.
CHAIRMAN KASS: Gil Meilaender?
PROF. MEILAENDER: What is luminously clear to our Chairman
is not necessarily so clear to me. So can you just explain to me
or help me be sure I'm clear, cleavage arrest correlates with
death of the embryo according to your proposed definition. And
that's the — so that's the test that you'd use
to determine whether an embryo was available for use in this way,
and would you therefore be using some embryos which were dead and
some which were conceivably still living according to your definition?
That's what I don't understand in terms of the correlation
DR. ZUCKER: They would be dead — if they're at 24
hours, they are not cleaving and 48 hours they're not cleaving,
those are dead. They wouldn't be — that's the concept that
they would be organismically dead at that point. It wouldn't be
that we would take cells that were then dividing further and try to
redefine that as being dead.
DR. LANDRY: And the precise moment, also is something
that's open to a natural history study and observation. So
the precise moment when, you know, a group of disinterested observers
would reasonably conclude that death has occurred is — and
to devise a definition for death, would occur as a result of observation
by analogy to observations of, you know, comatose patients.
DR. ZUCKER: And as Don mentioned in the presentation also
that we would be able to find specific markers to match up with
CHAIRMAN KASS: What begins as phenomenological account
of the natural history of this would then be supported by the discovery
of various kinds of biological markers that would give one confidence
that cleavage not only hasn't occurred, but isn't going
to occur. I think that's the —
PROF. MEILAENDER: So it was luminously clear to you and it
was luminously clear to you and not to me.
CHAIRMAN KASS: It was not luminously clear to you. Other
— yes, Robby George.
PROF. GEORGE: Thank you. I'm trying to see if I understand
what is new in what you're proposing and what is not new. It
sounds to me — and please correct me if I've misunderstood
you — it sounds to me as though you're not proposing a
new criterion of death or a different criterion of death. It sounds
as though the criterion of death you're proposing is what we
might now call the standard one of the complete and irreversible
loss of integrated or integral organic functioning. Is that right?
DR. LANDRY: I would call that the concept.
PROF. GEORGE: It's the concept of death.
DR. LANDRY: And then the criterion is what you take down
from that concept.
PROF. GEORGE: So the concept of death is the same whether
we're talking about, you know, an 80-year old person or we're
talking about an embryo.
DR. ZUCKER: Correct.
PROF. GEORGE: And so now what you're looking for is
what is the reliable evidence and I guess this you would then call a
criterion? All right, what is the reliable evidence of the complete
and irreversible loss of integrated organic functioning.
DR. LANDRY: Correct, so we would define it as arrested
cleavage and then the criteria for defining that arrested cleavage
would come down from that, a certain amount of time, the absence
of Oct4, you know, a series of biochemical markers in its fullest
PROF. GEORGE: Okay, so just again to be very clear,
there's no proposal here for a new concept of death —
DR. LANDRY: No.
PROF. GEORGE: — in order to accommodate the harvesting of
stem cells from embryos.
DR. LANDRY: No.
PROF. GEORGE: Okay, a second point, just a minor point
of clarification, I was interested in what you were saying about
the legitimacy of interventions on patients, and let's again
consider say an 80-year old person in extremis, that you were saying
there were circumstances in which it's ethically legitimate
to do certain things to patients in extremis that you couldn't
do to patients who were not in extremis. And I wonder if —
what the norms are governing those interventions. Are such interventions
legitimate but only when the purpose is to benefit or attempt to
benefit the patient himself, or is it sometimes permissible to do
some things to patients in extremis that you couldn't legitimately
do to patients not in extremis, not for the benefit of those patients
but for the benefit of others?
DR. ZUCKER: I guess one of those, you can use the analogy
of a chid who is critically ill lying there in an intensive care
unit and needs to be placed on let's say extracorporeal membrane
oxygenation or life support, and one may say at that point that
that person, you're doing a procedure on somebody and providing
a new therapy obviously through an IRB that you wouldn't routinely
do on other patients that weren't at that teetering on the edge,
and in the same way, we would feel that — as Don mentioned
before with the embryos in extremis, you could make that analogy.
PROF. GEORGE: Perhaps I'm being obtuse here, but —
DR. LANDRY: Since I've actually done this, maybe I can
PROF. GEORGE: Go ahead.
DR. LANDRY: Maybe I can just —
PROF. GEORGE: Please.
DR. LANDRY: Okay, we're dealing with patients in extremis
and by definition the intervention we're engaged in is not going
to benefit that patient. It is not anticipated that a patient in
the last few hours of life is going to be pulled from that moment
by the intervention. With the approval of the IRB, with the assent
of next of kin, it's possible to, for instance, provide experimental
drugs to observe their physiologic effect, understanding that it's
not a therapeutic effect.
PROF. GEORGE: I see. So it would be to benefit others and it
would be considered legitimate. But it wouldn't be considered
legitimate to do precisely the same thing if a patient were not
DR. LANDRY: Exactly.
PROF. GEORGE: And this is an accepted norm of medicine.
DR. LANDRY: Right, accepted norm.
CHAIRMAN KASS: Gil, I think, wants in on this subject.
PROF. MEILAENDER: Yeah, just the very same thing; you
wouldn't extract the organs of that infant, though, right?
DR. LANDRY: No, no, we're not talking about activities
that would kill or that would immediately hasten death, but activities
that might entail some risk and yet you would argue that, in the
last few hours of life, that risk is less than incremental to that
person at that time. Of course, if they're looking at the next
80 years of their life, then perhaps this is not a risk that should
be undertaken on their behalf. And so removing a cell from an embryo
that's about to expire, that activity not killing the embryo
necessarily although entailing a risk to that embryo if we wanted
to implant that embryo, we could take direct analogy from that activity
and the activity of experimentation in developed humans.
CHAIRMAN KASS: This really — this matter if I understand,
what you would be talking about would be the equivalent of single
blastomere biopsy that's used say in PGD which, though we haven't
had the studies to give us absolute confidence in this, there are
lots of children who have been born perfectly, apparently perfectly
normally, so that the removal of a biopsy or the removal of a cell
is already practiced in that case, I suppose you could say for the
benefit of that particular individual. Here you would not be adding
any extra risk and the act would be no more dangerous to that embryo
in extremis than that act is to an embryo that's headed for
implantation in the diagnostic procedure at PGD.
DR. LANDRY: Yes.
CHAIRMAN KASS: Is that —
DR. LANDRY: That's correct.
CHAIRMAN KASS: Now Gil.
PROF. MEILAENDER: But these are two different sorts of
justifications that you're thinking through. Am I right about
that? That is to say one sort of justification is if we have an
embryo that in terms of the criteria you've developed is dead,
we may use it in these ways. The other sort of justification is
that the rules for what we may do experimentally with a human organism
change when the organism though not dead is in extremis. That's
a different kind of justification. Am I correct on that?
DR. LANDRY: That's why I included it after the
PROF. MEILAENDER: Yeah, and that general issue there's
actually a long history of discussion and argument about and I would
be more inclined to worry about — I would want to think that
one through considerably more. It gets to do with the issue about
whether equal treatment must involve identical treatment, whether
you can wrong someone without harming them and various kinds of
questions like that and there is a long history of discussion about
that. So I just want to be clear, these are two different sorts
of justifications, and one might be persuaded by one but not the
other, for instance.
CHAIRMAN KASS: I want to turn to Bill, but only if there
aren't any questions to simply clarify what this proposal is
so that everybody should understand what Doctors Zucker and Landry
are proposing here. Alfonso and Jim Wilson, I think, have technical
questions rather than argumentative ones.
DR. GÓMEZ-LOBO: Yeah, this is, I think, a clarification
question. Of course, from a moral point of view, it seems to me
the idea of using cadaveric tissue for instance, should be less
problematic but I think we shouldn't forget that there's
going to be questions about the cause of the death or what led to
the death. I'm thinking out loud about the circumstance in
which say, a child or an older person is about to die, the death
is expected, in order to extract organs in circumstances, say, where
a rescue could have been possible. So I'm just leaving that
question open, because it is going to be ultimately of importance
for the moral judgment on the whole project.
CHAIRMAN KASS: Jim Wilson.
PROF. WILSON: Should your techniques prove with further
scientific inquiry to be valuable and the removal of non-viable embryos
can become a routine medical —
DR. LANDRY: Don't use the word "non-viable".
PROF. WILSON: I understand. What would you like? I like
DR. LANDRY: Organismically dead.
PROF. WILSON: Organismically dead, thank you. But at one
point in their history, they were —
DR. LANDRY: They were alive?
PROF. WILSON: Yes.
DR. LANDRY: If they were classified as non-viable, they
may have been dead, dying or doomed but we would restrict, you know,
our inquiry to those that are organismically dead.
PROF. WILSON: Organismically dead, fine. My question is,
should this procedure become widespread, what would be the source,
the principal source of these organismically dead entities?
DR. ZUCKER: The IVF embryos that are presently frozen that
then would be thawed for the purpose of creating life.
PROF. WILSON: And they would go through the test you've
DR. ZUCKER: Correct.
PROF. WILSON: Thank you.
CHAIRMAN KASS: Bill.
DR. HURLBUT: Can I ask you what stage of development you
anticipate most of these cells would come from?
DR. LANDRY: Eight to 12 cells.
DR. HURLBUT: It's my understanding that nobody's
ever seen a single eight-cell embryo lose seven of its blastomeres
as often happens after freezing and thawing, but is it absolutely
clear that a single cell from an eight-cell embryo cannot form a
DR. LANDRY: That's our understanding. And if evidence
came to the contrary, then we would move to 12 cells but the idea
is to avoid any question that that cell could by itself go on.
The loss of aggregate cytoplasm when you're dealing with a single
cell out of eight, would seem to preclude it.
DR. HURLBUT: Yeah.
CHAIRMAN KASS: Let's just stop on this and invite Bill
to make a presentation of his proposal and then we'll follow the
same procedure and we'll still have some time to discuss both of
these together and what we think about it.
DR. HURLBUT: Thank you. So what I want to say has some
similarity to the previous proposal. Death is the loss of potential
for future life through the disintegration of organismal life. What we
propose is the creation of entities that never rise to the level of
integrated organismal existence essential to be designated human life
with potential. I want to present some ideas that seem worthy of
discussion and possibly preliminary scientific investigation. Those of
us who have been working on these ideas have already explored some of
the philosophical and technical dimensions but there are important
theoretical and practical issues that need further consideration.
We offer these ideas not as an assertion of certitude but as a
promising avenue of inquiry, one that might move us beyond our current
conflict over the procurement of embryonic stem cells by providing
a third option, a technological solution to our moral impasse.
In the broadest sense, we propose a creative exploration of a full
range of scientific approaches. More specifically, we raise the
possibility that, using the technique of nuclear transfer, it may
be possible to produce embryonic stem cells within a limited cellular
system that is biologically and morally akin to a complex tissue
culture and thereby bypass moral concerns about the creation and
distruction of human embryos.
I want to make two points very clear from the beginning. What
is proposed here is a concept, an approach to a problem. The specific
examples, which may or may not be morally acceptable or scientifically
feasible, are offered only to make clear the larger concept as a
starting point for discussion. Second, we are at the stage of a
constructive dialogue; if these ideas are deemed feasible, extensive
studies with animal models must follow. We do not propose any projects
involving human cells until we can be certain that embryos are not
created by these methods.
The present conflict over the moral status of the human embryo reflects
deep differences in our basic convictions and is unlikely to be
resolved through deliberation or debate. May Americans oppose embryo
destruction for the procurement of embryonic stem cells, believing
that there is an implicit dignity and inviolability in the individual
continuity of a human life from fertilization to natural death.
Many others, however, believe that the benefits of advances in
biomedical science outweigh these moral concerns. A purely political
solution will leave our country bitterly divided, eroding the social
support and sense of noble purpose that is essential for the public
funding of biomedical science. While there are currently no federal
legislative constraints on the use of private funds for this research,
there is a consensus opinion in the scientific community that, without
NIH support for newly created embryonic stem cell lines, progress
in this important realm of research will be severely constrained.
Notwithstanding this apparently irresolvable impasse, we believe there
may be morally uncontroversial ways to obtain embryonic stem cells.
Drawing on our increasing understanding and control of developmental
biology, the techniques of altered nuclear transfer may allow us
to generate embryonic stem cells even apart from the organismal
system that is their natural origin. In order to evaluate the potential
solutions and allow forward progress within moral consensus, we
have to understand the perspectives and address the concerns of
those who believe that life begins at conception. By this view,
the most fundamental principle on which all other moral principles
are built is the intrinsic dignity and inviolability of human life
across all of its stages.
In both constitution and conduct, the zygote and all subsequent
embryonic stages differ from any other cell or tissues of the body.
They contain within themselves the organizing principle for the
self-development and self-maintenance of the full human organism.
The activation of an egg by the penetration of a sperm or the equivalent
events in nuclear transfer cloning procedures, triggers the transition
to active organismal existence with the potential to develop into
an adult human. But without all of the essential elements, the
necessary complement of chromosomes, proper chromatin configuration,
the cytoplasmic factors for gene expression, et cetera, there can
be no living whole, no organism and no human embryo. Recent scientific
evidence suggests incomplete combinations of the necessary elements,
failures of fertilization, are the fate of many, perhaps most early
natural initiations in reproduction. Altered nuclear transfer proposes
the artificial construction of such a cellular system mimicking
these natural examples, a system that lacks the essential elements
for embryological development but contains a partial developmental
potential capable of generating embryonic stem cells.
It is important to realize that many of these naturally
occurring failures of fertilization may still proceed along partial
trajectories of organic growth without being actual organisms. For
example, grossly abnormal karyotypes such as trisomies of Chromosome
Number 1, the largest chromosome with the most genes, you may know that
chromosomes are named by the largest to the smallest. These grossly
abnormal karyotypes will still form a blastocyst but will not implant.
Even an egg without a nucleus when artificially activated, has the
developmental potential to divide to the eight-cell stage; yet, clearly
is not an embryo or even an organism.
The messenger RNA in these activated enucleated cells has the protein
already in it, the protein synthesis that drives the early cell
divisions, it's generated during the maturation of the egg and
then activated after fertilization. Like a spinning top, the cells
contain a certain biological momentum that propels a partial trajectory
of development but unlike a normal embryo, they are unable to bootstrap
themselves into becoming an integrated and self-regulating organismal
Some of these aberrant products of fertilization that lack
the qualities and characteristics of an organism appear to be capable
of generating embryonic stem cells or their functional equivalent.
Mature teratomas are neoplasms that generate all three primary
embryonic germ cell types as well as more advanced cells and tissues
including partial limb and organ primordia and sometimes hair,
fingernails and even fully formed teeth. If you look at the
radiograph there, the little bright white areas to the left of the
spinal chord are teeth, fully formed teeth.
Yet these chaotic disorganized and non-functional masses lack
entirely the structural and dynamic character of organisms. These
benign ovarian tumors are is some cases derived by spontaneous and
disorganized development of activated eggs. They generally have
a complete karyotype, 46 XX, and they produce a diversity of cell
and tissue types that suggest that they may proceed through a developmental
process similar enough to natural embryogenesis to produce pluripotent
stem cells. In fact, through intentional parthenogenic activation
of monkey eggs, which mimics teratoma formation, one private US
company was able to coax them to a blastocyst-like stage and harvest
ES cells. Serious scholars and scientists including the geneticist
and Dominican priest, Nicanor Austriaco, have made serious moral
arguments supporting such a source of human ES cells. Furthermore,
there may soon be patent applications for such a procedure.
The disorganized character of teratomas appears to arise not from
changes in the DNA sequence but from genetic imprinting and epigenetic
modification that affects gene expression, keeping some genes turned
off and others on. In natural reproduction the sperm and egg have
different but complementary patterns of imprinting, allowing a coordinated
control of embryological development. When an egg is activated
without a sperm, the trophectoderm and its lineages fail to develop
properly and the differentiation of the trophectoderm and the inner
cell mass which forms the ES cells is considered to be the first
globally coordinated divergence into distinct cell lineages, so
it's an important indicator of organismal integrity and it lays
the pattern for the whole future of that organism. Nonetheless,
in this entity it fails to generate.
The trophectoderm is necessary for the cross-inductions that are
the foundation for all further coordinated and organismal growth
of the embryo. Later it contributes to the formation of the extra-embryonic
membranes, but early in development it is crucial for both embryo
structural integrity and for the development, continued development
at least, of a normal inner cell mass.
In the absence of the complementary genetic contribution of the
male, the activated egg is simply inadequately constituted to direct
the integrated development characteristic of human embryo genetic
process. Interestingly, an inverse failure of formation characterizes
development driven only by genetic elements from the male where
the complementary contribution of the female is missing. In hydatidiform
moles, an egg missing its nucleus is fertilized by one or more sperm
but this time, lacking the maternal genetic contribution with its
complementary imprinted genes, there is an over-growth of trophectoderm
with no apparent inner cell mass or embryonic stem cell-like cells
and little or nothing in the way of fetal parts.
Recent evidence suggests that in their development both of these
disorganized growths may proceed to the blastocyst stage. They
may appear on visual inspection to be growing normally but they
carry an intrinsic insufficiency, making them incapable of the essential
formation of body axis and infrastructure characteristic of human
embryogenesis. The cause of the aberrant and disordered growth
of these failures of formation is not fully understood, but studies
with parthenogenic mice provide a remarkable window into the organizing
or disorganizing role of a single genetic alteration.
Employing a form of altered nuclear transfer, Japanese scientists
produced a fully formed mouse using only female chromosomes but
with a single modification of an imprinted region to simulate the
necessary male contributions. They produced something that absolutely
can't happen in nature, just by modifying a single gene. With
— actually, it wasn't even a gene; it was a promoter region
expressing a gene — with this one change in genetic regulation,
directly affecting expression of just two genes downstream, instead
of disordered growth, normal offspring were produced and then to
everyone's amazement, the simple restoration of the male/female
complementarity of gene expression resulted in changes further downstream
of gene expression of over 1,000 other genes. This striking example
of our increasing power to intervene and alter natural processes
points to a coming era of challenging ethical dilemmas through advances
in developmental biology.
With new tools from cytology to synthetic biology, we are gaining
control of not just component parts and their partial trajectories
of growth but the very principles and dynamics of organismal systems.
Beyond highlighting our strange and challenging new powers over
developmental biology, the parthenogenic mouse points to another
level of advance in our understanding, our new appreciation of systems
biology in which we see how even a small change of one gene can
affect the entire balance of an enormous network of biochemical
processes within a cell. What's going on here? That's
too bad not to see that one [referring to a slide that did not project
Systems biology offers us the view of an organism as a living whole,
a dynamic network of inter-dependent and integrated parts. If severed
from the whole, these partial sub-systems may temporarily proceed
forward in development but, without the larger environment of their
organismal system, they will ultimately become merely disorganized
cellular growth. Altered nuclear transfer proposes that small but
precisely selected genetic alterations will allow the harnessing
of these sub-systems of partial development apart from their full
natural organismal context in order to produce embryonic stem cells.
Eventually, we will understand the biochemical factors that can
transform a somatic cell to a pluripotent state. But while the
ultimate goal for the generation of embryonic stem cells is the
direct nuclear reprogramming of an adult nucleus, it may be many
years before our scientific knowledge and control of cellular factors
will make this approach feasible. More immediately, we may be able
to use the techniques of nuclear transfer but with an intentional
alteration of the nucleus before transfer to the cytoplasm to construct
a biological entity that by design and from its very beginning lacks
the attributes and capacities of a human embryo.
Studies with mice already provide evidence that this altered nuclear
transfer may be able to generate functional embryonic stem cells
from a system that is not an embryo but possesses the limited organic
potential of a tissue or cell culture. For the sake of specifics
in this discussion, let me propose one particular example of how
this could be accomplished. This may not be an acceptable ultimate
solution but it will allow us to consider the necessary criteria
for scientific success and moral acceptability.
As well demonstrated in the work of Dr. Janet Rossant at Mount
Sinai Hospital in Canada, the gene cdx2 is essential for embryogenesis.
This gene is expressed immediately after compaction around the 16
to 32-cell stage and is crucial for the differentiation of the trophectoderm,
the outer layer of cells that seals the embryo and controls the
flow of water and ions into the inner cavity of the cell. Without
this, there's just an open space and the cell just can't
form its own integrity of an inside and an outside. Although the
trophectoderm is ultimately the source of embryonic membranes, it
is more properly considered part of the embryo as it plays a central
part in the interactive cell inductions that generate all subsequent
embryonic development. Studies confirm that a functional trophectoderm
is absolutely essential in embryogenesis. In experiments with mouse
models when cdx2 is not expressed, there is only a partial and disorganized
developmental process resulting in a visibly abnormal blastocyst.
Nonetheless, there is the formation of an inner cell mass from
which functional embryonic stem cells have been harvested as reported
in the May 2004 Proceedings of the National Academy of Sciences.
For the purposes of altered nuclear transfer, cxd2 might be deleted
from the somatic cell nucleus before transfer. Once the partial
embryonic stem cells have been generated, the gene in these cells
could then be reinstalled to allow fully potent embryonic stem cells.
This technologically created limited cellular subsystem from which
the embryonic stem cells would be obtained would fail to establish
even the most basic features of human organismal infrastructure.
A deficiency at the first differentiation of cell type, the formation
of the trophectoderm, means the absence of the most fundamental
order. According to Dr. Maureen Condic, a developmental biologist
at the University of Utah, she says, "When the trophoblast,"
which is immediately after the trophectoderm, "when the trophoblast
does not form, subsequent development follows a chaotic pattern
suggesting that organismal development has not been disrupted in
the absence of the trophoblast but rather that an organism never
existed in the first place."
The resulting cells would have no inherent principle of unity
— that is, the entity produced, not the embryonic stem cells,
but the entity produced would have no inherent principle of unity,
no coherent drive in the direction of the mature human form and
no claim on the moral status due to a developing human life. Rather,
such a partial disorganized organic potential would more readily
be designated a biological artifact, a term I owe to my colleague,
Paul McHugh, when talking about early discussions of cloning. This
entity would be more rightly designated a biological artifact,
a human creation for human ends. The fact that some part of such
a constructed entity will carry a certain momentum of development
is morally analogous to the fact that we can grow skin in a tissue
culture and may one day grow whole organs or limbs in isolation.
Lacking crucial elements of its fundamental constitution, such an
entity would never rise to the level of a living being.
The scientific prospects for altered nuclear transfer remain largely
unexplored but, as stated by Rudolf Jaenisch in testimony to this
council, they are already within the reach of our current technology.
Unlike other proposals, ANT — I'm calling this alternate
nuclear transfer ANT — ANT would allow a uniquely flexible
approach by providing a wide range of embryonic stem cell types
that would have the full normal complement of human chromosomes,
would be of specific genetic types for tissue-compatible transplantation
and would not carry the danger of contamination from animal components.
In addition, this technique would offer a far wider range of scientific
and medical possibilities than embryonic stem cell lines derived
from leftover IVF embryos, including generation of diverse and predesigned
embryonic stem cell lineages for disease modeling and pharmaceutical
Indeed, in allowing controlled and reproducible experiments, altered
nuclear transfer might serve as a temporary bridge to transcendent
technologies such as direct nuclear reprogramming. Furthermore,
in establishing a morally acceptable means for the procurement of
embryonic stem cells, this important realm of scientific investigation
would be open to federal funding and have the advantage of both
broad public support and cooperative research collaboration on a
Altered nuclear transfer would also unburden ES cell research
from the additional ethical concerns of the leftover IVF embryos
including the attendant clinical and legal complexities in a realm
of great personal and social sensitivity. The one remaining link
with in vitro fertilization, the procurement of oocytes is the subject
of intense scientific research and there appear to be several prospects
for obtaining eggs without the morally dubious and expensive superovulation
of female patients, the specifics of which we can discuss later
if you want.
The crucial principle of any technological variation of altered
nuclear transfer, however, must be the pre-emptive nature of the
intervention. This process does not involve the creation of an
embryo that is then altered to transform it into a non-embryonic
entity. Rather the proposed genetic alteration is accomplished
ab initio, the entity is brought into existence with a genetic structure
insufficient to generate a human embryo. From the beginning and
at every point along its development, it cannot be designated a
living being. If such a limited biological entity were accorded
a certain cautionary respect, as with all human tissues, this project
would not compromise any fundamental moral principle. Moreover,
such techniques could be developed using animal models and confidently
extended to work with human cells without engaging in research that
involves the destruction of human embryos. The moral distinctions
essential to discern and define the categories of organism, embryo
and human being will inevitably be vital as we go forward with scientific
research involving human embryonic stem cells, chimeras and laboratory
studies of fertilization and early embryogenesis. Advances in developmental
biology will depend on clarifying these categories and defining
the moral boundaries in a way that at once defends human dignity
while clearing the path for scientific progress.
At this early stage in our technological control of developing life,
we have an opportunity to break the impasse over stem cell research
and provide moral guidance for the biotechnology of the future.
This may require a constructive refinement of some aspects of moral
philosophy together with creative exploration of scientific possibilities,
but any postponement of this process will only deepen the dilemma
as we proceed into realms of technological advance unguided by forethought.
We must initiate the cooperative dialogue that is essential to frame
moral principles that can, at once, defend human dignity and promote
the fullest prospects for scientific progress and its medical applications.
CHAIRMAN KASS: Thank you very much, Bill. As before,
we'll just direct questions to Bill for technical clarification
but also certain moral questions. I'm sure some people might
have some. Jim Wilson, please.
PROF. WILSON: Bill, thank you very much. Could you
describe for us now the scientific procedure you or someone else would
follow and the entities on which they would work that would test the
viability of this theory?
DR. HURLBUT: Well, we already know that you can take,
at least in this example I gave, that you can take an entity which
— from which you can get disorganized growth and yet functional
embryonic stem cells. What we would have to do is — I think
the first thing that would happen is, there should be a very thorough
discussion about what the criteria to meet both the moral concerns
and functional scientific goals would be. Once those were decided,
you would have to see if you could do it. And the way to do this
would be, and I have scientists including Evan Snyder at the Burham
Institute in San Diego who are interested in working on this and
enthusiastic about the idea. You would have to start with mice,
probably — they're the easiest and quickest to work with
— and just go through the genes that might be of interest
and they could probably do this fairly easily because you can use
— for the initial research, you can use techniques called
short interfering RNA, which are very easy to apply and do a first
scan to see what genes might serve the functional purposes that
we want. Doing it fully and officially with human cells, you might
want to knock out the gene, a technique that I've checked out
with my colleagues, Ron Davis, who's head of the Human Genome
Technology Center at Stanford and Andy Fire, who basically invented
RNA interference, these scientists both confirm that to be finally
and ultimately sure the best way to do this is likely to be the
knockout and then replacement of the gene, but the preliminary studies
could be done with short interfering RNA. You could scan through
many, many possible genes, and by the way, gene combinations to
double and complementarily assure your success and refine your technique.
Then I think it would have to — once you identified
something that worked in mice, you'd have to move on to primates
which has already been done, as I mentioned, harvesting of embryonic
stem cells but you'd have to do the knockout and then the
harvesting to see if it worked and the thinking is among all the
developmental biologists I've spoken with, that there is such a
conservation of biology of these developmental genes and developmental
processes that we could, with assurance, go forward with human cells
without the fear of creating a human embryo.
PROF. WILSON: Which human cells would you use?
DR. HURLBUT: That is probably going to be dictated by
which human cells most effectively go forward with nuclear transfer.
It appears that some cells are better than others. Cumulus cells
are what they used in South Korea. They're the cells around
the egg during its development. We would have to use a cell, if
we were going to knock out the gene, a cell that multiplied through
numerous cycles in vitro because you want to be sure you've
got the gene knocked out, but I think that's just a technical
problem and it wouldn't be that hard to do and there's great
advance going on constantly in this technique of nuclear transfer.
CHAIRMAN KASS: Questions of clarification on the technical
side first so that we — I want to make sure that everybody here
understands precisely what it is that Bill is proposing. Gil and then
PROF. MEILAENDER: Bill, I'm just trying to think this through,
and let's just suppose hypothetically that you could, through
some technique, produce an entity which had the capacity to implant
but would absolutely not develop beyond eight weeks something like
that, how would that procedure — and I realize that may never
— perhaps that would never be technically possible, but just
suppose you could produce an entity which from the start is characterized
that way, how would that differ from what you're proposing?
DR. HURLBUT: Well, that's an important question and
I might add that one — what I think one of the positive dimensions
of my proposal is that for the concerns that these techniques might
lead to implantation of human embryos perfected through this technique
and surreptitiously implanted without the genetic alterations, it's
important to note that these cells produce, if it's done with
a gene knockout and replacement, would carry a bar code that would
identify them as having undergone this transformation, but to get
to your central issue — in other words, it would not lead
to human reproductive cloning in the sense of child-producing.
To get to your fundamental question, you're saying will this
not lead us to push the process forward and say well, this wasn't
an organized human entity and so forth. That's a very challenging
question. What level of organization defines an organism? I've
gone back to what is considered the primary tissue differentiation
of the organism and by the way, these would be abnormal from the
beginning as are also all nuclear transfer cells. Some of them
are abnormal to the extent they can right themselves.
As we saw in the paper that, as presented earlier, nuclear transfer
greatly disrupts the gene expression patterns. But we would have
to be certain that this was to the very most primary level of disrupted
organismal organization. And I think there is some scientific thinking
to be done, but I think we should turn to scientists to help us
with that. I think we have to be very careful that the principle
we set up does not allow it to be pushed forward to regions that
are — that evoke our natural moral sentiments and to the most
minimal possibility. What's being said is we want embryonic
CHAIRMAN KASS: You follow, Gil.
PROF. MEILAENDER: Yes, I'm still just trying to think
through the description, kind of. You're talking about producing
an entity that appears — I mean, the kind of language you
use — and I might not get this quite adequately translated,
but it's about an entity that appears to be growing normally but
really lacks the capacity to continue that development beyond a
certain point. And again, I'm just thinking analogously. Could
I use that same sentence about a child born with Tay-Sachs disease?
I'm not trying — I'm just trying to think —
could we say of that same child — of that child that it appears
to be growing normally but lacks the capacity for continued development
beyond a certain point? I'm just trying to think through where
that kind of language goes and I may not have the language technically
sophisticated enough and you know, that may be part of what you
want to say to me but what — how would you answer that?
DR. HURLBUT: I mean, that's a very important question
but to — I think to think clearly about that question you
have to have some sense of how the organismal process unfolds.
There is a — as I said earlier, there is a certain momentum
of substance in the egg. There's a certain kind of primordial
automaticity to the way things happen initially. Without the coordinated
interaction of subsystems as I tried to show in the systems biology,
you just simply can't go there. I think it's a difference,
an ontological difference between something that never organizes
itself in what is meaningfully called an organism and I don't
mean meaningfully like they say in Marin County in California.
I mean rightly by scientific criteria not organizing itself in the
minimal constructions. And what those would actually be would
have to be clearly and carefully worked out by both scientists and
moral philosophers but I would include at the very least one or
maybe several of these entities and I would think at least it should
not be able to form the infrastructure and body plan of a human
That's — I think that's too far. I would go back
to the most primary lineage differentiation and I don't think
that's analogous to a fully formed self-evidently human entity.
I mean, there's been a big debate about whether an anencephalic
baby is a human person. I think it's self-evident. If not
a human person in the full sense of what it is, it has a radiance
of respect due to it just by its humanness somehow, its human likeness.
And I don't — those are very difficult definitional terrains,
but let me say again, we are heading into this terrain inevitably
whether this proposal goes forward or not. We're creating hybrid
human animal creatures. We're going to generate human parts
apart from the whole. We're going to have to start doing the
hard work of defining what is the minimal construction of a moral
entity called a human being.
CHAIRMAN KASS: Look, can I intervene? It seems to me
this — I don't want to dissent from what Bill has just
said, but on the limited question that you asked, I don't think
you need to go in that full theoretical direction to say —
he's given you a couple of examples here of things that grow
on their own, teratomas and hydatidiforms cysts which are developing
but are not organisms. And I think anything that you would say
that gets to develop to be a fetus at eight weeks with the human
form is not a mole and it's not a cyst. But Bill, I think
what we want to say is what we're talking about here is not
an organism and not a being, in the same way as a cyst or a mole
is not a being. It's not just that it will not develop further.
It's not a developing thing. It's a thing — there
is growth that takes place here but it is not an organism, growth
in the sense of increase but there isn't somehow a pre-given
form that is being developed in the way an eight-week old embryo
would and I don't think you need — and I think that's
sort of descriptively accurate without having to get into ontological
questions. You don't really have a being here, in the same
way as those moles and things —
DR. HURLBUT: Let me show you something interesting on this
slide. This is — on the top is a normal human embryo forming. On the
bottom is an embryonic stem cell in a culture forming a so-called
embryoid body. I mean, it's not identical but what I use this for
is to show that there are biological qualities within just the
chemistry, the cell that will organize to some degree. And so
organization, per se, is not — is not indicative of organism in the
meaningful sense of the word. There's — biology has a certain
self-organizing power. So —
PROF. MEILAENDER: And what is indicative of organism?
It's not just growth but it's also not organization?
DR. HURLBUT: It is organization but it's organization of
the species- typical kind.
PROF. MEILAENDER: Okay.
CHAIRMAN KASS: Paul McHugh and then Mike Gazzaniga.
DR. McHUGH: Well, Bill has talked with me several times
before about this. It's nice to hear the whole thing laid out,
and I still have some technical questions. I don't want to
talk about the ethical issues right at the moment, because they
are deep and important, but I do, with Gil, want to follow along
on this terminological business because at one level this procedure
that you propose to us, and we've talked about before, is really
to build a weird genetic hybrid that in its next steps of development,
call it what you will, that next steps of development, would lack
the features that would render it ultimately viable as an independent
organism. Isn't — first of all, is that right?
This is a strange genetic hybrid that you've made but it —
and it's going to go through a process, a process of embryonic-like
development built in as it is —
DR. HURLBUT: Partial.
DR. McHUGH: — and you don't want to call that an
embryo because you said it doesn't have the potential for full
DR. HURLBUT: Well, it doesn't have the actual at any
level that is embryo-like. It's different.
DR. McHUGH: Well, it's very embryo-like. I mean,
that's the whole thing about these hydatidiform moles for that
matter, is that they are embryo-like.
DR. HURLBUT: Well, okay, embryo-like but embryo truly?
DR. McHUGH: No, and now we're back right at square
one again. Do you want to call everything that follows along this
developmental process an embryo or not, and the real issue with
SCNT right from the start as we've discussed before, and that
Rudy Jaaenisch tended to emphasize was that, in point of fact, it
differed from in vitro fertilization in that its origins were not
through fertilization but through this remarkably different process
so that no new creature had appeared and, as well, it lacked the
potential at least in the primate form of ever getting through the
pregnancy and therefore, perhaps by your definition, it also cannot
be called an embryo, and if it cannot be called an embryo, but rather
a source for embryonic stem cells, is it listed?
That gets us into the ethical problem. I just want to be sure
I understand that the process that you are proposing here is fundamentally
to interfere with the nucleus, with the genome, really, of these
things so that you have made a genetic hybrid. Now to come to the
ethical problem, we have just heard our Canadian friends tell us
that you cannot make, under their laws, a chimera or a hybrid with
in vitro fertilization or other kinds of things, and they reject
This would seem to be making a deadly hybrid and therefore, might
be saluted in this purpose but it would be an opening to make —
to propose or make — the process of making a new model chimera
or hybrid which would be super-human in some kind of way and therefore,
enter a domain that — I haven't finished my thoughts on
this because this is so important what you're telling us, Bill,
this is very, very important stuff but at the same time, I begin
to get — a few red flags begin to come up for me over what
we have done and or what we're thinking of doing here and what
it might mean.
DR. HURLBUT: Well, Paul, let me make one comment about that.
I'm not suggesting you create a deadly hybrid. To be —
to use that term, you'd have to say that the thing was alive
first. The point is, you do this ab initio. You never —
you create an entity that never rises to the level of what can properly
be called a living being.
DR. McHUGH: That brings us back to the point I made about
our friends here. It brings us back to our friends here. They are
very — they want to use what you want to use, the organismically
integrated organism and are very fearful of the use of the word
"non-viable" unless by their definition non-viable means
dead, dying or doomed. Those are a rattle of Ds that I thought were
very helpful to me in thinking about this process. Well, what you have
done is made a doomed hybrid, doomed.
DR. HURLBUT: Not doomed. Only doomed if it's alive
DR. McHUGH: Well, it's doomed in the sense that it
will never get out.
DR. HURLBUT: Well —
DR. McHUGH: Develop.
DR. HURLBUT: — you mean somebody with only potential,
like any chemicals mixed together.
DR. McHUGH: No, no, that these are cells — they want to
make the point that non-viable means, as I understand it, I'd refer
back to Dr. Landry and Dr. Zucker, who brilliantly presented their
views on the concept of death and discussed it nicely with Robby. They
want to make the — they want to use your point of organismically
integrated as being the issue of — the concept of death but they want
to not use the word non-viable because the cells they want are, of
course, viable. They want to use those cells, at least as I've
understood the conversation this morning in relationship to life
processes and life organization and systems. But as I say, I'm
still groping here.
CHAIRMAN KASS: Paul, can I try to help, Bill? Look, Doctors
Landry and Zucker don't like the language of non-viable here
because there are things which are non-viable which are still alive
and to use them might be to kill them. They want an embryo —
they want to develop criteria for embryonic death that would make
this exactly analogous to the determination of death in a developed
being. But the reason that they insist on those criteria is because
they know perfectly well that what they're starting with is,
in fact, a being of a human sort and alive, which will be first
doomed by somebody's decision, and then, if they can develop
the criteria, can be pronounced dead.
That doesn't apply to the way Bill is speaking because what
Bill is talking about doesn't yet rise to being a living human
being. The cells are of human origin and that says they're
human. But no more than is a hydatidiform mole a human being would
Bill's re-engineered entity be an organism. It would simulate
certain organic activities, in the sense that there would be cell
division, but it would have been engineered in such a way that you
couldn't — if you understood what you were doing and what
you have done, you could not call it a living human embryo. It
would be embryo-like only in the sense that it went through certain
stages of cell division but it would not be embryonic in the sense
that it had no — it was incapable ab initio of being embryonic
in the sense that it is pointed toward and developing — it
is not a being to begin with, with that kind of future.
And I think for me the question is, can you make such
things. It seems to me it's a technical question less than it is a
philosophical one if I have understood what he has told us.
PROF. GEORGE: You mean more than it is.
CHAIRMAN KASS: I'm sorry.
PROF. GEORGE: More than it is. A technical question more
than a philosophical one. In other words, you're saying it's
not really a philosophical question, it's a technical.
CHAIRMAN KASS: Yeah, exactly. Yeah, I'm sorry. Mike
DR. GAZZANIGA: Well, we're not capable of — first of
all, thanks, Bill. I appreciate what you're trying to do and I
think it's admirable. In many ways, I'd just like to make a
couple of observations, it does say to us that we do need more stem
cell lines and —
DR. HURLBUT: More what?
DR. GAZZANIGA: More stem cell lines. We need more lines
if we're going to get this job done. Why else would we be torturing
ourselves with this proposal. The — I do take exception and
I just want to bring a little clarity to those of us who don't
have this deep moral dilemma with using a 14-day old blastocyst
to harvest stem cells and therefore the need for this bio-engineering
project. And the other point I want to make, is that what we're
trying to do here, it seems to me, is, normally, we generate a word
to describe a biologic phenomenon and here we seem to be tinkering
with biologic phenomenon to have it fit the meaning of a word, and
that's not what you do.
So this rests a little bit back to Paul's point of two years
ago and basically the question underlying now is you are building
something here and we're going to have to call it something.
And it's not an embryo, it's something else if you want
to have it play out this way. And finally, I would just say, I
— because of my position on the moral status of a 14-day old
blastocyst, that has no brain, so we don't have to worry about
brain dead and all that sort of stuff — I forgot what I was
going to say. What was I going to say? Oh, that — excuse
me, I'm sorry, that the money and investment and time and trying
to develop a science of this, postpones, if we were doing it serially,
what we now know how to do, what I gather will be going forward
in the State of California and many other nations that — that's
right, well, many of them not as big as California, that it has
the risk, and I'm sure you've thought about this, of delaying
the important advances that could come from the sort of research
to alleviating pain and suffering and people who surely would like
DR. HURLBUT: Mike, I don't even understand how you
make laws. I start all my classes at Stanford by saying, "We're
going to not really talk about laws in this class. We're going
to talk about ideals, what we should do if we could", and
I quote that saying, "Never ask what goes into sausages and
laws". I truly do not raise this issue with a political agenda.
I raise it with the desire to see our society go forward, in both
forward progress in science, and forward progress in our moral thinking.
You say we need new embryonic stem cell lines. I think
with — if the scientific goals are the ones we're after, I agree
with that. As far as I've been able to understand from my
colleagues, I'm not a stem cell biologist, but I think it was
obvious that when the President put forward his policy, we would seek
moral ways to get new embryonic stem cell lines. So I don't think
any reasonably educated person in science is going to contend with
that, but at the same time we also need to confirm and solidify those
moral principles that will help us go forward into increasingly complex
terrains with development biology and if you could say that progress
walks forward on two legs, one technical and one moral, we need to
solve this — in my opinion we need to solve this in a way that we can,
as human beings, as a collective, cooperative society in a way that
creatively and intelligently recognizes that neither side in this
debate is — nobody is a fool in this debate. Both sides are upholding
important human goods and the amazing thing is there might be ways to
do this so that we could both be confirmed in the positive things
we're trying to defend.
CHAIRMAN KASS: Okay, Dan, and after Dan, I want to suggest
that we be thinking about the general conversation while we consider
both of these proposals and I would like to know what the council
thinks of either or both of this general direction. We can't
settle that today, but Dan, please, first.
DR. FOSTER: Yeah, I only want to make a brief statement
and I'm one of the minority, you know, in the original thing
but it seems to me that one of the fundamental principles that we
started off in this discussion about the bioethical concern was
that you had a series — you had two sets of goods. You had
two sets of goods, and one of them has to be dominant and the other
one did not in the 10 to 7 vote, but the principle that I think
that Bill is working on here and others is that this may be a way
to accomplish both of these goods without violating either of the
issues which are there, so I think it's a — and I'm
not worried about the cost because I believe that scientists always
learn things if you're working with one of these, what, "new
creations" or whatever you want to call it. We're going
to learn things that are also powerfully important.
I don't think you're going to have any dearth of scientists
that want — that would not want to explore this. Whether
it's going to work, I mean, the whole issue, I mean, from Dolly
on, as we were talking about, you know, I mean, it's really
hard to get — you know, to do this sort of stuff. I mean,
it took 270, 280 attempts to do it. The Koreans took — you
know, so there are many technical problems but that's what science
is all about. So I would say, to me, this is a very attractive
way to remove the issues that were of major concern about destroying
human life and at the same time, extending the stem cell things
where we can get diseased molecules and things of that sort, so
I'm adding my side in contrast to some of the view, in very
strong support, not of any technical aspects of this, but the principle
that one might be able to accomplish both of these goods with some
model like Bill or the Columbia people have put forward.
CHAIRMAN KASS: If I might, I would be interested in
hearing from especially the people we haven't heard from what you
think about this, Diana, Peter, Alfonso, Robby, Mary Ann, Jim Wilson.
DR. LAWLER: Let me ask Bill, what's your objection to
the other proposal which is basically to work with dead embryos?
DR. HURLBUT: Well, it's not really an objection.
In fact, by the way, if you can get embryonic stem cells out of
eight-cell morula, my project is a snap. I'm not sure you can.
I know Verlinski claims to have done that but the stem cell biologists
I've talked to say that at least at this point we don't
know how to coax them up and that they are more primordial cells
still, but maybe that's true. You know, the one thing we just
have to stop doing is being so narrow in our view of what science
can accomplish. I mean, science is a wonderfully creative process
and can yield for us all sorts of new ways to do things that we
have concerns about one direction, get them another way. I basically
think this is wonderful thinking at the heart of this proposal and
by the way, I'd be perfectly happy if my proposal was bypassed
by other easier, more practical ones and I think that eventually
Every stem cell biologist I talked to has told me that they
think it's just a little period here we have to get through
eventually to understand all of this well enough to create these
entities with no moral concerns at all. Is that what you asked me?
DR. LAWLER: Well, right, so the answer would be the
question is, which is more possible then.
DR. HURLBUT: Which is more possible?
DR. LAWLER: Yeah, which proposal can —
DR. HURLBUT: I mean, that's anybody's call but we
don't have any markers for the death of these things and when you
say that at 24 hours of rest, 10 percent still go onto 48 hours, that
is a little bit of a problemmatic moral question. You've in a way
endorsed in vitro fertilization in the first place. That would be a
problem for some people. You've got a limited number of cell types
you can work with. You've got the question that Paul put forward
and it's not a trivial question, whether even a mosaic, a normal
appearing karyotype from a mosaic cell may still have something in the
constitutional cell that provoked the aneuploidy in the first place.
There's some evidence that aneuploidy is promoted by certain
factors in the developmental powers of the cell themselves, although
it may just be pushing the growth too fast. But these are all really
fundamental questions... but again, they're technical questions.
The moral principles that were put forward before me I think make
sense. If something is not integrated, if it does not have the
principle of life in it, that's what we're trying to defend.
We're not trying to defend parts of things. We have to find
the locus of our concern. In the twentieth century, we came to
terms with the fact — I'm sorry — we came to terms
with the fact that cells like in transfusions were not the moral
locus of the person, although some cultures still believe that.
We came to terms with the idea that genes were not the locus. We
put human genes into bacteria. We learned that organ transplants
I was at Stanford Medical School when the first heart transplant was
done and some people were saying, "Well, that's just too
much of the person, or that's the person". It took a few
months and we figured that that wasn't the — in this area
of developmental biology, we're going to learn that seemingly
alive, partial trojectories of organic growth without the full integrated
principle of life organizing unity of their organismal context,
are not — even if they're human I'm speaking of, without
that principle of life, they are not moral entities.
CHAIRMAN KASS: Look there are people who have to make
a plane and we also have a public comment session, so I really want
— if anybody wants to — we're not forced here to
choose between these things. The question is, does the concept
appear to the council, knowing that the technical questions are
not in our hands to determine, and I don't think — I'd
rather not have arguments for the proposal as much as I would like
to hear, from the people who haven't spoken, what they think
DR. LAWLER: I completely agree with what Dan said on this,
it's a promising area to explore, bound to benefit us and resolve
a question that might not be resolved any other way.
CHAIRMAN KASS: Diana?
DR. SCHAUB: Yeah, it seems to me almost too good to be
true that scientific advance — well, that scientific advance itself
would solve these moral dilemmas, and if — I mean, I guess I am
persuaded that you are not creating an embryo and therefore, it
doesn't trigger my concern about the equality principle. I guess
the only question I would have, I think it does not trigger that
concern about equal treatment of all human beings because you're
not creating a human being. Is there any concern that you were doing
something even more radical than that, namely, that you're
tampering with the organizing principle of, I don't know of life
itself. I mean, is there —
DR. HURLBUT: I think that principle is only of moral concern
only when it's instantiated in a living human being. What I'm
trying to do here is define more clearly the boundaries of our moral
concern and that's what I'm saying, it's the integrated
G.K. Chesterton has a beautiful little metaphor, little
boys are playing soccer on a field but right at the edge of a field
there are cliffs that go down 2,000 feet to the crashing waves on the
rocks below, so where are they playing soccer, in the middle 20 yards
of the field. And then somebody comes and draws a clear line at the
borders, puts up a fence and they can play to the field.
Right now, and even more in the future, if we don't define
these moral boundaries clearly, we're going to impede forward
progress in science or many people are going to feel like moral
purposes are being violated, moral goods are being violated. We
need to do that hard work of defining these boundaries, but I think
the meaningful boundary is the integrated human organism at all
of its stages, and just make one sentence more: I, as everybody
in this council knows, have stood very strongly for the principle
that human life is present from conception. When I looked at the
scientific facts — and I didn't come in like some rubber
stamp agent of this counsel to do what somebody told me to do —
I looked as plainly as I could and I simply could not think —
could not agree that the early embryo was, as some scientists are
saying, an inchoate clump of cells. It's a living whole human
CHAIRMAN KASS: Bill, look, I think we've had your
elaboration on this and I really do want to get people who have to
leave, their comments on the record, so if you'd hold back until
we've heard from Jim and Mary Ann and Alfonso and I want to have a
word, too. Jim.
PROF. WILSON: I support this venture for all the reasons
that have been indicated. I do agree with Mike that you have to find a
name for this. It's extremely important. We can't go around
saying we're producing ANTs because the ant lovers — the name is
already used and widely admired by some close friends of mine. But we
have to find a name for it. Being a gardener, I would call what
we're doing as producing weed, not an animal and not a desirable
plant but I certainly support the venture.
CHAIRMAN KASS: It's not weed in the California sense.
CHAIRMAN KASS: Mary Ann. Jim, thank you.
PROF. GLENDON: Well, I think that this may turn out to be
one of the most fruitful meetings that the council has had and I'm
very grateful to both of — all three of the presenters. I think a
problem for some of us is we don't want to get over-excited about
these indications that there may be a path through the thicket of
technical and moral problems that we've been struggling with for so
long but I think you've all been so careful and nuanced and at
least as clear to us lay people as it's probably possible to be
although I — with Gil I can't pretend that I followed everything,
but I do think that this may be the beginning of very, very significant
turn in our history. So thank you very much.
CHAIRMAN KASS: Alfonso.
DR. GÓMEZ-LOBO: At present, my thinking is still
hypothetical on both proposals. On the Columbia University proposal,
if I may call it like that, of course, if indeed the extraction of the
cells proceeds from a dead organism, I would say that's morally
viable and extremely interesting. I'm sure there has to be a lot
of refinement in terms of the concept of death of the criteria and the
actual tests, I mean, the empirical evidence.
With regard to Bill's proposal, we've talked a lot
about it and I'm very close to the affirmation of the conditional
hypothetical question, but of course, there has to be a lot more
elaboration in the sense of making it very clear to the public that
we're not talking here about mutilation, because that's, I
think, what is lurking in the back of many people, whether what's
going on here may be the moral equivalent of generating a human embryo
but you just knock some genes so that it becomes non-viable, which
was Rudolph Jaenisch's position. I remember discussing it with him
and I insisted that we had to distinguish between genetic modification
that makes an organism non-viable from a genetic modification that made
it non-human and I think that's very important. Now, your
argument, Bill, is an argument fortiori at present.
DR. HURLBUT: A what?
DR. GÓMEZ-LOBO: A fortiori —
DR. HURLBUT: Yes, I get it.
DR. GÓMEZ-LOBO: — in the sense that since it's not an
organism, therefore, it cannot be a human organism. It seems to me
that that concept has to be refined in terms of what would be necessary
and sufficient conditions for the organism to be human. I know that
that's a major, major enterprise, but I think both proposals are
very, very interesting, worth pursuing.
CHAIRMAN KASS: Robby George.
PROF. GEORGE: Thank you, Leon. Bill, it's always seemed
critical to me in this debate that the embryo is a whole living
member of the species homo sapiens at the earliest stage of his
or her natural development. It's also always seemed clear to
me and I've seen no one here or elsewhere dispute this, that
a hydatidiform mole or a teratoma is not a whole living member of
the species of the homosapiens at any developmental stage.
So it seems to me that the whole ball game as far as your
proposal is concerned is the question whether an entity created by the
altered nuclear transfer process would be the equivalent of a
hydatidiform mole or teratoma or would be a severely damaged embryo or
an embryo programmed for an early death and I think this goes to the
heart of what Gil raised originally. Now, when I ask myself why are we
so sure that a teratoma is not a whole living member of the species
homosapiens, why are we so sure we can distinguish the teratoma from an
embryo, my conclusion is that the teratoma, unlike the embryo, lacks,
you know, from the start and always, the active disposition for
self-organization and self-directed development in the direction of
There may be additional things we can say about that but it
seems that we begin by saying at least that much.
Now, is it critical to you that we not go forward with your proposal,
at least with ANT, at least in humans, until we've reached moral
certainty that in fact, the product would be analogous to a hydatidiform
mole or teratoma rather than to an embryo? Is that critical to
DR. HURLBUT: Yes, it is.
PROF. GEORGE: So you, yourself, would not want to see the
proposal go forward unless it could be shown that in the human case, we
would not be creating an embryo.
DR. HURLBUT: Yeah, that would violate the very principle
we're trying to defend.
PROF. GEORGE: Right. Animal experimentation then would be
critical to determining whether, in fact, the entities created are
DR. HURLBUT: Yes.
PROF. GEORGE: — truly non-embryonic in which case,
I think then you're saying that all you're proposing to
us is animal experimentation to determine whether when we examine
the products of ANT we have on the basis of our, you know, biochemical
and molecular examination entities that are truly analogous to teratomas
or hydatidiform moles and therefore, are non-embryonic, no more
than that, right?
DR. HURLBUT: Yes, that's right.
PROF. GEORGE: So you're not proposing that we do this
in human beings now. That proposal has gone on the table.
DR. HURLBUT: Absolutely no.
PROF. GEORGE: Okay, one other very brief line of questions;
you have used as an example of a method of ANT the switching off
of the cdx2 gene which would then be switched on later when the
stem cells are derived. That possible method was described in an
article in The Boston Globe by the science writer Gareth
Cook recently. And my own e-mail tells me that a lot of people
interpreted what was said in that article to imply that ANT just
is the method involving switching off cdx2. But I thought I heard
you say today, and you can correct me if I'm wrong, I thought
I heard you say today that that method is simply one of perhaps
any of a number of possible methods of altered nuclear transfer
which you, yourself, think has some promise but may turn out to
be inadequate to the task of creating a truly non-embryonic entity
in which case you would look to another method.
DR. HURLBUT: Yes, or a combination of methods with great
surety. See, it doesn't have to be just one thing. SiRNA, you can
put several in at once. You can knock several genes out if you have to,
just maybe a little more complicated, but you know, the idea is that
we've beginning to understand the biology of development enough to
determine to some degree what is going on with teratomas. And if we
biologically could artificially mimic that or some equivalent of it
that was ontologically equivalent, that would be what I would be after.
PROF. GEORGE: So the method involving the switching off of cdx2
could prove in the animal experimentation to be inadequate to the
project of producing a truly non-embryonic entity, in which case
you would abandon that as a morally legitimate method of ANT if
used in humans.
DR. HURLBUT: Oh, yes, I didn't put the one project
forward with the specific gene as anything but an example of how
amazing it is that you can get a fully normal functional embryonic
stem cell out of an entity that is grossly abnormal, with a trophectoderm
not forming in that entity, the thing doesn't even hold together
— the inner cell mass over-grows the center of the blastoseal,
the cavity of the blastocyst — and yet, you still get functional
cells out of it. That was why I used that example, but I specifically
am not tied to any one gene or any suggestion at this point. I'm
proposing an exploration of this.
PROF. GEORGE: Thank you.
CHAIRMAN KASS: We are just about at the end and want to have
the public comment session. Let me put my own thoughts on the record
and also make a proposal to the residual of the council. I know
people have had to go to catch planes, but if you — the Communist
party's slogan was to come to the meeting early and stay late
and those of us who stay till the end can actually approve the next
procedures, but I think these are two extremely interesting, extremely
interesting, very creative proposals, absolutely worth not only
our consideration but much more public consideration. Bill has
been working on this for two years and has consulted enormously
widely with moral leaders and religious leaders and with scientists
and there has been a tremendous amount of encouragement.
And I was a foot-dragger on this, not so much on moral but aesthetic
grounds, not altogether unrelated to the point raised by Diana,
and I'm not sure that the aesthetic objection turns on whether
or not this thing is or is not the organismic entity. But that
objection, I think has been overcome by the sense of the real promise
of this, and I, myself, am prepared at least in principle to endorse
it and eager to see the details worked out scientifically.
This other proposal, which has also been a long time in gestation,
and very, very carefully thought out and very subtly now refined
and clear conceptually also strikes me as extremely exciting. It
should not be too hard to do this kind of research, starting in
the mice or starting in various kinds of things, and to begin to
look for these criteria. And it seems to me that for this council
and the public generally what would be most encouraging, is if,
in the course of the next several months, we could begin to receive
some kind of information on some specific suggestions on where the
science might be or some kind of protocols or suggestions for where
the science could go, so that if we indeed mean to endorse this
as a morally fruitful possibility for the nation to go, we could
also back it up with some kind of practical information on that:
"this is not just a nice idea, but might be feasible, if the
following kinds of steps are taken." I think both of you are
prepared to do this and have the information. It didn't —
since this was the first airing in this gathering, it wasn't
probably the time to get all that scientific detail out there.
By the way, just accidentally, although one doesn't generally
regard the New Scientist or BBC News as a scientific
publication, there is this report that human eggs have now been
developed parthenogenetically, with the expectation that we will
get to the blastocyst stage, using just an enzyme derived from sperm,
in which the whole process goes on along. There are no male chromosomes
in this thing and there's an almost certainty that this will
not go on — could not go on — to develop into a child,
and this might be yet another route, another morally non-problematic
route to getting the kinds of — to getting us to the point
of getting new embryonic stem cell lines.
So I want to thank the three of you for — not just for the
presentations today but for the enormously serious and careful and
thoughtful work that has gone into bringing these proposals forward,
the consultations that you've taken and the evolution of these two
separate projects which I've known about really since almost the
beginning. And I think the council and the nation are really in your
debt for trying to find a way forward that does not involve the — if
successful, would not require anybody who's party to this debate to
sacrifice anything of great importance. So thank you very, very much.
Gentlemen, you may be excused but you're also free to sit
here. We have two people who want to make public comment and they
might, in fact, be on this, so if you have five to 10 minutes, we
have a public comment from Jaydee Hanson of the International Center
for Technology Assessment, followed by Richard Doerflinger of the
United States Conference of Catholic Bishops. Do you want to take
the microphone there?
SESSION 7: PUBLIC COMMENTS
MR. HANSON: Well, thank you for the opportunity to comment
today. The Executive Director of the Center wanted me to extend his
personal greetings to you, Dr. Kass. So greetings from Andrew
Kimbrell. I want to say my comments are going to be on the altered
nuclear transfer technique and I want to begin by offering my personal
words to Bill and how much I appreciate his thoughtful thinking.
But, we're told that this procedure is intended as a means of avoiding
the destruction of embryos in producing embryonic stem cells, but
we think this notion is mistaken in that we believe that the technique
actually does produce embryos albeit defective ones through a combination
of cloning and human germline and genetic engineering. We think
if the proposed experiment were to be conducted on human embryos,
it would confront us with an ethical question about whether we produce
any human life solely for its commercial value.
We also think there's a second ethical watershed that
would be crossed. This would be in effect, the first human germline,
genetic engineering experiment. For the first time, we would be
engineering human life at its earliest stages. In fact, it seems to
require two engineerings. We do not believe that society should cross
these boundaries without a very full public debate. We urge the
council to support an immediate moratorium on all such experiments with
human embryos until a robust public debate has occurred and there is
wide public consensus that we have in place safeguards to prevent abuse
of this potential technology.
We go on and list some other concerns we have but those are
out two main concerns and I thank you for your time.
CHAIRMAN KASS: Thank you very much and hold it just a
second. If there is a longer statement either now or soon, I think
this would be welcome and we'll see that it's circulated to
everybody here. The genetic modification aspect of this is an issue
that so far hasn't been discussed today and whether or not this is
or is not an organism or an embryo, there are people who have reason to
be concerned about such genetic engineering close to the human and I
think the point — it's something we will want to talk about.
MR. HANSON: We also, just to briefly summarize the longer
point, we also have some concerns that this — even if the proponents
don't consider this an embryo, they may well want to patent it.
The patent office might consider in embryo-like enough to use it as a
precedent. So we have other concerns as well.
CHAIRMAN KASS: Thank you very much.
MR. HANSON: I do have copies of the statement I'll
leave with whoever.
CHAIRMAN KASS: If you'd just leave it with Diane
Gianelli, she'll see that all of us get sent this. Thank you very
MR. HANSON: Thank you very much.
CHAIRMAN KASS: Richard Doerflinger.
MR. DOERFLINGER: I also want to talk about altered nuclear
transfer. I have — as many on the council know — have
been skeptical and remain skeptical of many claims for the unique
benefits of embryonic stem cells, including those derived from nuclear
transfer. That being said, I know many scientists believe in those
unique benefits, and some of them share my moral convictions against
destroying human life at any stage.
If, and this is a big if, a procedure can be found to provide
embryonic stem cells without creating or destroying embryos, that
would address the Catholic Church's most fundamental moral objection
to embryonic stem cell research as now pursued. Clearly, such a
procedure would not be prohibited by the cloning bans the Catholic
bishops have supported at the state or federal level, which routinely
exempt the use of nuclear transfer or any other cloning procedure
to produce tissues, organs or cells other than human embryos.
I, therefore, see no moral reason at this time to oppose the further
exploration of this theory in an animal model so its feasibility
can better be assessed. This would give scientists an opportunity
to show their real commitment is to scientific progress, not to
the exploitation of embryos, and gives organizations like mine an
opportunity to show that our concern is respect for life, not a
fear of scientific research or scientific progress.
Regarding one particular technique for pursuing this, the deletion of
the cdx2 gene, I for one am not convinced it fulfills my criterion
for saying the resulting entity is never an embryo. Surely, it
is not enough to say the genetic defect preventing organismal development
was introduced into the genome from the very beginning. Any adult
who develops Huntington's disease at the age of 40 had the genetic
defect ab initio. But it also matters what development has taken
place in the meantime.
If that gene is expressed only after the 16 to 32-cell
stage, it seems to me this would be an embryo that undergoes normal
development as a human organism to a certain point and then dies.
Surely the entity has to depart from organic human development from the
beginning to fulfill what I would see as the correct goal for altered
If no procedure can be found that truly produces embryonic stem
cells but not an embryo, my objections would certainly be equal
to some of those raised by Mr. Hanson.
Finally, the problem of using human eggs and the potential of exploiting
women for their eggs will ultimately have to be addressed once this
is attempted in humans. Perhaps animal eggs will turn out to be
sufficient. Those have proved very disappointing to researchers
trying to use cloning to make normal human embryos using animal
eggs, but here we are not trying to make normal human embryos.
Perhaps very few eggs of any kind will be needed, because this
technique will be used chiefly to make a few cell lines as disease
models or for drug testing. Increasingly, proponents of cloning
for research are admitting that large scale use of nuclear transfer
to make cells for direct therapeutic use in patients is doomed to
practical and economic failure. I would only note that it would
have been nice for them to admit that before they managed to convince
the voters of California to approve the $3 billion give-away for
cloning last month. Or perhaps other ways to achieve complete or
partial reprogramming of a body cell nucleus without using an egg
will be further refined and replace the use of eggs for this technique.
I do simply want to offer the caveat that this problem ultimately
must be addressed as well, the problem of use of human eggs, if
this approach is to achieve moral consensus. But at this time, I
certainly appreciate the conceptual model that Dr. Hurlbut has presented,
and I think exploration in animal models is well worth at least
pursuing at this time. Thank you.
CHAIRMAN KASS: Since you have the floor and since you are
really one of the most meticulous and thoughtful and careful people
about such things and even though you didn't come prepared to speak
about it, do you have any reaction to the other proposal of developing
criteria for death in embryos follow — only following which would the
removal of embryos be attempted? Does that strike you as morally
acceptable, questionable? Do you have — or would you rather think
about it and let me know privately?
MR. DOERFLINGER: I would rather think about it. I came
in late and was not here for the presentation and have not read
the materials, and I will certainly study that as well. Anything
that achieves the promised scientific benefits without exploiting
or destroying human life is something that the Church wants to have
an open mind to, so I will certainly study that as well.
CHAIRMAN KASS: Thank you very much. I think we've
done everything that we hoped to do at this meeting and more. I thank
our guests especially. Thanks to council members. Thanks to the
members of the public and the meeting is adjourned.
(Whereupon, at 12:13 p.m. the above entitled